dbSNP rs7204371: ACD:c.242+9C>T (chr16-67659894-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001082486.2(ACD):c.242+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,432,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ACD
NM_001082486.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.36

Publications

5 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 Gene-Disease associations (from GenCC):

dyskeratosis congenita, autosomal dominant 6
Inheritance: AR, AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P
hereditary isolated aplastic anemia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Hoyeraal-Hreidarsson syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACD links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ACD	NM_001082486.2 link	c.242+9C>T	intron_variant	Intron 2 of 11	ENST00000620761.6	NP_001075955.2	Q96AP0-3
ACD	NM_022914.3 link	c.233+9C>T	intron_variant	Intron 2 of 11		NP_075065.3	Q96AP0-2
ACD	NM_001410884.1 link	c.242+9C>T	intron_variant	Intron 2 of 10		NP_001397813.1
ACD	XR_429728.4 link	n.282+9C>T	intron_variant	Intron 2 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACD	ENST00000620761.6 link	c.242+9C>T		intron_variant	Intron 2 of 11	1	NM_001082486.2	ENSP00000478084.1		Q96AP0-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000140

AC:

AN:

1432102

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

708712

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33008

American (AMR)

AF:

0.00

AC:

AN:

43232

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24698

East Asian (EAS)

AF:

0.00

AC:

AN:

39262

South Asian (SAS)

AF:

0.00

AC:

AN:

83714

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47764

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5672

European-Non Finnish (NFE)

AF:

9.13e-7

AC:

AN:

1095632

Other (OTH)

AF:

0.0000169

AC:

AN:

59120

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

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

5.9

(source)

DANN

Benign

0.94

PhyloP100

-1.4

PromoterAI

-0.13

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over