Genetic Variant SMARCAD1:c.190+290G>T (chr4-94208874-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_020159.5(SMARCAD1):c.190+290G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0126 in 152,094 control chromosomes in the GnomAD database, including 19 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 0.013 ( 19 hom., cov: 31)

Consequence

SMARCAD1
NM_020159.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.526

Publications

9 publications found

Variant links:

Genes affected

SMARCAD1 (HGNC:18398): (SWI/SNF-related, matrix-associated actin-dependent regulator of chromatin, subfamily a, containing DEAD/H box 1) This gene encodes a member of the SNF subfamily of helicase proteins. The encoded protein plays a critical role in the restoration of heterochromatin organization and propagation of epigenetic patterns following DNA replication by mediating histone H3/H4 deacetylation. Mutations in this gene are associated with adermatoglyphia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

SMARCAD1 Gene-Disease associations (from GenCC):

ectodermal dysplasia syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: Illumina
isolated congenital adermatoglyphia
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
palmoplantar keratoderma-sclerodactyly syndrome
Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: G2P, Orphanet
absence of fingerprints-congenital milia syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SMARCAD1 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=-0.84).

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0126 (1909/152094) while in subpopulation SAS AF = 0.0247 (119/4822). AF 95% confidence interval is 0.0211. There are 19 homozygotes in GnomAd4. There are 952 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 1909 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCAD1	NM_020159.5 link	c.190+290G>T		intron_variant	Intron 2 of 23	ENST00000354268.9	NP_064544.2	Q9H4L7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCAD1	ENST00000354268.9 link	c.190+290G>T		intron_variant	Intron 2 of 23	1	NM_020159.5	ENSP00000346217.4		Q9H4L7-1

Frequencies

GnomAD3 genomes

AF:

0.0126

AC:

1908

AN:

151976

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00278

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0111

Gnomad ASJ

AF:

0.0265

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0245

Gnomad FIN

AF:

0.0178

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0174

Gnomad OTH

AF:

0.0163

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

GnomAD4 genome

AF:

0.0126

AC:

1909

AN:

152094

Hom.:

Cov.:

AF XY:

0.0128

AC XY:

952

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.00277

AC:

115

AN:

41466

American (AMR)

AF:

0.0111

AC:

170

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0265

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.0247

AC:

119

AN:

4822

European-Finnish (FIN)

AF:

0.0178

AC:

188

AN:

10582

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0174

AC:

1186

AN:

67972

Other (OTH)

AF:

0.0161

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

198

298

397

496

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.00111

Hom.:

9638

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.1

(source)

DANN

Benign

0.59

PhyloP100

0.53

Mutation Taster

=100/0

polymorphism

(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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over