Genetic Variant SMARCAD1:c.368+106C>T (chr4-94226402-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_020159.5(SMARCAD1):c.368+106C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 24 hom., cov: 18)

Exomes 𝑓: 0.038 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

SMARCAD1
NM_020159.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.31

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 4-94226402-C-T is Benign according to our data. Variant chr4-94226402-C-T is described in ClinVar as [Benign]. Clinvar id is 1253074.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0345 (4217/122306) while in subpopulation AFR AF= 0.0481 (1548/32156). AF 95% confidence interval is 0.0461. There are 24 homozygotes in gnomad4. There are 2056 alleles in male gnomad4 subpopulation. Median coverage is 18. This position pass quality control queck.

BS2

High AC in GnomAd4 at 4217 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCAD1	NM_020159.5 link	c.368+106C>T		intron_variant	Intron 3 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.368+106C>T		intron_variant	Intron 3 of 23	1	NM_020159.5	ENSP00000346217.4		Q9H4L7-1

Frequencies

GnomAD3 genomes

AF:

0.0344

AC:

4208

AN:

122304

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0480

Gnomad AMI

AF:

0.0255

Gnomad AMR

AF:

0.0216

Gnomad ASJ

AF:

0.0440

Gnomad EAS

AF:

0.0332

Gnomad SAS

AF:

0.0168

Gnomad FIN

AF:

0.0415

Gnomad MID

AF:

0.0509

Gnomad NFE

AF:

0.0300

Gnomad OTH

AF:

0.0304

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0382

AC:

12673

AN:

331916

Hom.:

AF XY:

0.0388

AC XY:

6898

AN XY:

177740

show subpopulations

Gnomad4 AFR exome

AF:

0.0533

Gnomad4 AMR exome

AF:

0.0442

Gnomad4 ASJ exome

AF:

0.0491

Gnomad4 EAS exome

AF:

0.0357

Gnomad4 SAS exome

AF:

0.0454

Gnomad4 FIN exome

AF:

0.0730

Gnomad4 NFE exome

AF:

0.0327

Gnomad4 OTH exome

AF:

0.0373

GnomAD4 genome

AF:

0.0345

AC:

4217

AN:

122306

Hom.:

Cov.:

AF XY:

0.0359

AC XY:

2056

AN XY:

57296

show subpopulations

Gnomad4 AFR

AF:

0.0481

Gnomad4 AMR

AF:

0.0217

Gnomad4 ASJ

AF:

0.0440

Gnomad4 EAS

AF:

0.0331

Gnomad4 SAS

AF:

0.0169

Gnomad4 FIN

AF:

0.0415

Gnomad4 NFE

AF:

0.0300

Gnomad4 OTH

AF:

0.0308

Alfa

AF:

0.134

Hom.:

327

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.19

DANN

Benign

0.19

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over