Genetic Variant ENST00000547247.5:n.1300G>A (chr12-50089138-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000547247.5(SMARCD1):n.1300G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 152,120 control chromosomes in the GnomAD database, including 8,586 homozygotes. 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: 𝑓 0.31 ( 8582 hom., cov: 32)

Exomes 𝑓: 0.23 ( 4 hom. )

Consequence

SMARCD1
ENST00000547247.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.777

Publications

13 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000547247.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCD1	NM_003076.5	MANE Select	c.771+501G>A		intron	N/A	NP_003067.3
	SMARCD1	NM_139071.3		c.771+501G>A		intron	N/A	NP_620710.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SMARCD1	ENST00000547247.5	TSL:1	n.1300G>A	non_coding_transcript_exon	Exon 6 of 6
SMARCD1	ENST00000394963.9	TSL:1 MANE Select	c.771+501G>A	intron	N/A	ENSP00000378414.4
SMARCD1	ENST00000381513.8	TSL:1	c.771+501G>A	intron	N/A	ENSP00000370924.4

Frequencies

GnomAD3 genomes

AF:

0.313

AC:

47622

AN:

151914

Hom.:

8554

Cov.:

show subpopulations

Gnomad AFR

AF:

0.398

Gnomad AMI

AF:

0.291

Gnomad AMR

AF:

0.369

Gnomad ASJ

AF:

0.318

Gnomad EAS

AF:

0.771

Gnomad SAS

AF:

0.382

Gnomad FIN

AF:

0.261

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.219

Gnomad OTH

AF:

0.304

GnomAD4 exome

AF:

0.227

AC:

AN:

Hom.:

Cov.:

AF XY:

0.220

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AF:

0.375

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.156

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.314

AC:

47684

AN:

152032

Hom.:

8582

Cov.:

AF XY:

0.322

AC XY:

23904

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.399

AC:

16529

AN:

41456

American (AMR)

AF:

0.370

AC:

5653

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.318

AC:

1103

AN:

3464

East Asian (EAS)

AF:

0.771

AC:

3985

AN:

5168

South Asian (SAS)

AF:

0.381

AC:

1836

AN:

4822

European-Finnish (FIN)

AF:

0.261

AC:

2753

AN:

10554

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.219

AC:

14852

AN:

67970

Other (OTH)

AF:

0.304

AC:

641

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1609

3218

4826

6435

8044

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

464

928

1392

1856

2320

<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:

0.251

Hom.:

4704

Bravo

AF:

0.326

Asia WGS

AF:

0.524

AC:

1821

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.3

(source)

DANN

Benign

0.59

PhyloP100

0.78

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over