Genetic Variant NM_003076.5:c.1269+192G>A (chr12-50094764-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_003076.5(SMARCD1):c.1269+192G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 152,066 control chromosomes in the GnomAD database, including 5,745 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.25 ( 5745 hom., cov: 33)

Consequence

SMARCD1
NM_003076.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.47

Publications

6 publications found

Variant links:

Genes affected

SMARCD1 (HGNC:11106): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily d, member 1) The protein encoded by this gene is a member of the SWI/SNF family of proteins, whose members display helicase and ATPase activities and which are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI and has sequence similarity to the yeast Swp73 protein. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

SMARCD1 Gene-Disease associations (from GenCC):

Coffin-Siris syndrome 11
Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
Coffin-Siris syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SMARCD1 links:

ENSG00000295262 (HGNC:):

ENSG00000295262 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 12-50094764-G-A is Benign according to our data. Variant chr12-50094764-G-A is described in ClinVar as Benign. ClinVar VariationId is 1282660.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCD1	NM_003076.5 link	c.1269+192G>A		intron_variant	Intron 10 of 12	ENST00000394963.9	NP_003067.3	Q96GM5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCD1	ENST00000394963.9 link	c.1269+192G>A		intron_variant	Intron 10 of 12	1	NM_003076.5	ENSP00000378414.4		Q96GM5-1

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

37913

AN:

151948

Hom.:

5737

Cov.:

show subpopulations

Gnomad AFR

AF:

0.175

Gnomad AMI

AF:

0.320

Gnomad AMR

AF:

0.343

Gnomad ASJ

AF:

0.317

Gnomad EAS

AF:

0.771

Gnomad SAS

AF:

0.382

Gnomad FIN

AF:

0.260

Gnomad MID

AF:

0.226

Gnomad NFE

AF:

0.218

Gnomad OTH

AF:

0.270

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.249

AC:

37921

AN:

152066

Hom.:

5745

Cov.:

AF XY:

0.259

AC XY:

19288

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.175

AC:

7263

AN:

41458

American (AMR)

AF:

0.343

AC:

5250

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.317

AC:

1099

AN:

3472

East Asian (EAS)

AF:

0.771

AC:

3996

AN:

5184

South Asian (SAS)

AF:

0.381

AC:

1834

AN:

4818

European-Finnish (FIN)

AF:

0.260

AC:

2748

AN:

10554

Middle Eastern (MID)

AF:

0.216

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.218

AC:

14807

AN:

67974

Other (OTH)

AF:

0.270

AC:

570

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1398

2796

4193

5591

6989

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

398

796

1194

1592

1990

<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:

0.229

Hom.:

5292

Bravo

AF:

0.254

Asia WGS

AF:

0.507

AC:

1761

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 16, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.055

(source)

DANN

Benign

0.67

PhyloP100

-3.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over