rs1050346

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_001082486.2(ACD):c.1336C>T(p.Leu446Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000317 in 1,614,176 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L446L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0017 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

ACD
NM_001082486.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.482

Publications

0 publications found

Variant links:

Genes affected

ACD (HGNC:25070): (ACD shelterin complex subunit and telomerase recruitment factor) This gene encodes a protein that is involved in telomere function. This protein is one of six core proteins in the telosome/shelterin telomeric complex, which functions to maintain telomere length and to protect telomere ends. Through its interaction with other components, this protein plays a key role in the assembly and stabilization of this complex, and it mediates the access of telomerase to the telomere. Multiple transcript variants encoding different isoforms have been found for this gene. This gene, which is also referred to as TPP1, is distinct from the unrelated TPP1 gene on chromosome 11, which encodes tripeptidyl-peptidase I. [provided by RefSeq, Jul 2008]

ACD links:

CARMIL2 (HGNC:27089): (capping protein regulator and myosin 1 linker 2) This gene encodes a member of the CARMIL (capping protein, Arp2/3, myosin-I linker) family of proteins. The encoded protein interacts with and negatively regulates the heterodimeric capping protein and promotes cell migration. Reduced expression of this gene has been observed in human psoriasis patients. Mutations in this gene cause a human immunodeficiency syndrome characterized by smooth muscle tumors and impaired T-cell function. [provided by RefSeq, May 2017]

CARMIL2 Gene-Disease associations (from GenCC):

severe combined immunodeficiency due to CARMIL2 deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

CARMIL2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 16-67657647-G-A is Benign according to our data. Variant chr16-67657647-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 434065.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.482 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001082486.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACD	NM_001082486.2	MANE Select	c.1336C>T	p.Leu446Leu	synonymous	Exon 12 of 12	NP_001075955.2	Q96AP0-3
ACD	NM_022914.3		c.1327C>T	p.Leu443Leu	synonymous	Exon 12 of 12	NP_075065.3	Q96AP0-2
ACD	NM_001410884.1		c.1249C>T	p.Leu417Leu	synonymous	Exon 11 of 11	NP_001397813.1	A0A8Q3WM11

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACD	ENST00000620761.6	TSL:1 MANE Select	c.1336C>T	p.Leu446Leu	synonymous	Exon 12 of 12	ENSP00000478084.1	Q96AP0-3
ACD	ENST00000695659.1		c.1354C>T	p.Leu452Leu	synonymous	Exon 12 of 12	ENSP00000512089.1	A0A8Q3SHY1
ACD	ENST00000219251.13	TSL:2	c.1327C>T	p.Leu443Leu	synonymous	Exon 12 of 12	ENSP00000219251.8	Q96AP0-2

Frequencies

GnomAD3 genomes

AF:

0.00168

AC:

256

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00596

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.000466

AC:

117

AN:

251276

AF XY:

0.000405

show subpopulations

Gnomad AFR exome

AF:

0.00610

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000174

AC:

254

AN:

1461822

Hom.:

Cov.:

AF XY:

0.000166

AC XY:

121

AN XY:

727214

show subpopulations

African (AFR)

AF:

0.00648

AC:

217

AN:

33480

American (AMR)

AF:

0.000425

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53358

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1112004

Other (OTH)

AF:

0.000232

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00169

AC:

257

AN:

152354

Hom.:

Cov.:

AF XY:

0.00176

AC XY:

131

AN XY:

74508

show subpopulations

African (AFR)

AF:

0.00596

AC:

248

AN:

41578

American (AMR)

AF:

0.000327

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68040

Other (OTH)

AF:

0.00189

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000883

Hom.:

Bravo

AF:

0.00196

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Dyskeratosis congenita, autosomal dominant 6 (2)

ACD-related disorder (1)

Inborn genetic diseases (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

2.9

(source)

DANN

Benign

0.91

PhyloP100

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over