4-94291034-A-G

Position:

• chr4-94291034-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020159.5(SMARCAD1):​c.*1500A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 437,872 control chromosomes in the GnomAD database, including 44,195 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 0.38 (11896 hom., cov: 32)
  • Exomes 𝑓: 0.46 (32299 hom.)
• Consequence: SMARCAD1 NM_020159.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• 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.*1500A>G		3_prime_UTR_variant	24/24	ENST00000354268.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCAD1	ENST00000354268.9	c.*1500A>G		3_prime_UTR_variant	24/24	1	NM_020159.5	P4
SMARCAD1	ENST00000359052.8	c.*1500A>G		3_prime_UTR_variant	24/24	1		A1

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57518 AN: 151836 Hom.: 11877 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.369

GnomAD3 exomes AF: 0.487 AC: 60105 AN: 123494 Hom.: 15662 AF XY: 0.487 AC XY: 32486 AN XY: 66764

Gnomad AFR exome AF: 0.242

Gnomad AMR exome AF: 0.623

Gnomad ASJ exome AF: 0.397

Gnomad EAS exome AF: 0.707

Gnomad SAS exome AF: 0.580

Gnomad FIN exome AF: 0.387

Gnomad NFE exome AF: 0.403

Gnomad OTH exome AF: 0.437

GnomAD4 exome AF: 0.461 AC: 131684 AN: 285918 Hom.: 32299 Cov.: 0 AF XY: 0.469 AC XY: 76354 AN XY: 162660

Gnomad4 AFR exome AF: 0.242

Gnomad4 AMR exome AF: 0.625

Gnomad4 ASJ exome AF: 0.390

Gnomad4 EAS exome AF: 0.719

Gnomad4 SAS exome AF: 0.570

Gnomad4 FIN exome AF: 0.385

Gnomad4 NFE exome AF: 0.403

Gnomad4 OTH exome AF: 0.430

GnomAD4 genome AF: 0.379 AC: 57546 AN: 151954 Hom.: 11896 Cov.: 32 AF XY: 0.386 AC XY: 28684 AN XY: 74276

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.481

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.714

Gnomad4 SAS AF: 0.588

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.397

Gnomad4 OTH AF: 0.377

Alfa AF: 0.396 Hom.: 13128

Bravo AF: 0.382

Asia WGS AF: 0.629 AC: 2185 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.2
DANN	Benign	0.65

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: rs8026; hg19: chr4-95212185;