4-94232198-T-C

Position:

• chr4-94232198-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.369-1756T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 150,778 control chromosomes in the GnomAD database, including 12,714 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 0.40 (12714 hom., cov: 32)
• Consequence: SMARCAD1 NM_020159.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCAD1	NM_020159.5	c.369-1756T>C		intron_variant		ENST00000354268.9	NP_064544.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCAD1	ENST00000354268.9	c.369-1756T>C		intron_variant		1	NM_020159.5	ENSP00000346217.4

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60437 AN: 150664 Hom.: 12691 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.716

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.386

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

GnomAD4 genome AF: 0.401 AC: 60477 AN: 150778 Hom.: 12714 Cov.: 32 AF XY: 0.408 AC XY: 30065 AN XY: 73718

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.491

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.715

Gnomad4 SAS AF: 0.587

Gnomad4 FIN AF: 0.386

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.393

Alfa AF: 0.238 Hom.: 563

Bravo AF: 0.403

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.7
DANN	Benign	0.34

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: rs3106136; hg19: chr4-95153349;