4-94290459-T-C

Variant summary

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

The NM_020159.5(SMARCAD1):c.*925T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 454,208 control chromosomes in the GnomAD database, including 81,785 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 0.57 (25034 hom., cov: 32)
  • Exomes 𝑓: 0.61 (56751 hom.)
• Consequence: SMARCAD1 NM_020159.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34

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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMARCAD1	NM_020159.5	c.*925T>C		3_prime_UTR_variant	24/24	ENST00000354268.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCAD1	ENST00000354268.9	c.*925T>C		3_prime_UTR_variant	24/24	1	NM_020159.5	P4
SMARCAD1	ENST00000359052.8	c.*925T>C		3_prime_UTR_variant	24/24	1		A1
SMARCAD1	ENST00000457823.6	c.*925T>C		3_prime_UTR_variant	24/24	1		A1

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86846 AN: 151896 Hom.: 25012 Cov.: 32

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.559

GnomAD3 exomes AF: 0.620 AC: 84352 AN: 136028 Hom.: 26541 AF XY: 0.617 AC XY: 45596 AN XY: 73874

Gnomad AFR exome AF: 0.491

Gnomad AMR exome AF: 0.725

Gnomad ASJ exome AF: 0.533

Gnomad EAS exome AF: 0.708

Gnomad SAS exome AF: 0.635

Gnomad FIN exome AF: 0.563

Gnomad NFE exome AF: 0.586

Gnomad OTH exome AF: 0.589

GnomAD4 exome AF: 0.609 AC: 184089 AN: 302192 Hom.: 56751 Cov.: 0 AF XY: 0.610 AC XY: 105082 AN XY: 172242

Gnomad4 AFR exome AF: 0.501

Gnomad4 AMR exome AF: 0.726

Gnomad4 ASJ exome AF: 0.531

Gnomad4 EAS exome AF: 0.723

Gnomad4 SAS exome AF: 0.631

Gnomad4 FIN exome AF: 0.570

Gnomad4 NFE exome AF: 0.590

Gnomad4 OTH exome AF: 0.594

GnomAD4 genome AF: 0.572 AC: 86918 AN: 152016 Hom.: 25034 Cov.: 32 AF XY: 0.577 AC XY: 42877 AN XY: 74312

Gnomad4 AFR AF: 0.498

Gnomad4 AMR AF: 0.641

Gnomad4 ASJ AF: 0.535

Gnomad4 EAS AF: 0.718

Gnomad4 SAS AF: 0.636

Gnomad4 FIN AF: 0.572

Gnomad4 NFE AF: 0.587

Gnomad4 OTH AF: 0.565

Alfa AF: 0.586 Hom.: 45368

Bravo AF: 0.573

Asia WGS AF: 0.679 AC: 2363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	13
Dann	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs8336; hg19: chr4-95211610;