rs11722476

chr4-94249688-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2 BP4_Strong BP6_Very_Strong BA1

The NM_020159.5(SMARCAD1):c.740G>A(p.Ser247Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 1,602,518 control chromosomes in the GnomAD database, including 148,090 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.38 (11860 hom., cov: 31)
  • Exomes 𝑓: 0.42 (136230 hom.)
• Consequence: SMARCAD1 NM_020159.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.176

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]

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• PP2: Missense variant where missense usually causes diseases, SMARCAD1
• BP4: Computational evidence support a benign effect (MetaRNN=1.8179811E-6).
• BP6: Variant 4-94249688-G-A is Benign according to our data. Variant chr4-94249688-G-A is described in ClinVar as [Benign]. Clinvar id is 1286948.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-94249688-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMARCAD1	NM_020159.5	c.740G>A	p.Ser247Asn	missense_variant	7/24	ENST00000354268.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCAD1	ENST00000354268.9	c.740G>A	p.Ser247Asn	missense_variant	7/24	1	NM_020159.5	P4

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57383 AN: 151356 Hom.: 11840 Cov.: 31

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.367

GnomAD3 exomes AF: 0.467 AC: 117053 AN: 250898 Hom.: 29521 AF XY: 0.466 AC XY: 63242 AN XY: 135606

Gnomad AFR exome AF: 0.235

Gnomad AMR exome AF: 0.636

Gnomad ASJ exome AF: 0.394

Gnomad EAS exome AF: 0.708

Gnomad SAS exome AF: 0.581

Gnomad FIN exome AF: 0.393

Gnomad NFE exome AF: 0.401

Gnomad OTH exome AF: 0.428

GnomAD4 exome AF: 0.423 AC: 613556 AN: 1451044 Hom.: 136230 Cov.: 31 AF XY: 0.427 AC XY: 308711 AN XY: 722566

Gnomad4 AFR exome AF: 0.229

Gnomad4 AMR exome AF: 0.620

Gnomad4 ASJ exome AF: 0.391

Gnomad4 EAS exome AF: 0.756

Gnomad4 SAS exome AF: 0.576

Gnomad4 FIN exome AF: 0.391

Gnomad4 NFE exome AF: 0.400

Gnomad4 OTH exome AF: 0.414

GnomAD4 genome AF: 0.379 AC: 57412 AN: 151474 Hom.: 11860 Cov.: 31 AF XY: 0.387 AC XY: 28612 AN XY: 73974

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.482

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.715

Gnomad4 SAS AF: 0.588

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.397

Gnomad4 OTH AF: 0.374

Alfa AF: 0.404 Hom.: 31926

Bravo AF: 0.382

TwinsUK AF: 0.394 AC: 1462

ALSPAC AF: 0.398 AC: 1533

ESP6500AA AF: 0.243 AC: 1071

ESP6500EA AF: 0.390 AC: 3353

ExAC AF: 0.456 AC: 55327

Asia WGS AF: 0.628 AC: 2179 AN: 3468

EpiCase AF: 0.387

EpiControl AF: 0.394

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Keratoderma with scleroatrophy of the extremities Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Basan syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

This variant is associated with the following publications: (PMID: 22864933) -

Adermatoglyphia Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.80
Cadd	Benign	13
Dann	Benign	0.78
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.54	D
MetaRNN	Benign	0.0000018	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.20	N;N;N
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.74	N;N;N
REVEL	Benign	0.20
Sift	Benign	0.50	T;T;T
Sift4G	Benign	0.49	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.033
MPC		0.28
ClinPred		0.0033	T
GERP RS		0.20
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.046

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

Other links and lift over

dbSNP: rs11722476; hg19: chr4-95170839; COSMIC: COSV62773013; COSMIC: COSV62773013;