rs728989

Positions:

• chr4-94243330-G-C
• chr4-94243330-G-T

Variant summary

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

The NM_020159.5(SMARCAD1):​c.705+2324G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 152,126 control chromosomes in the GnomAD database, including 35,593 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 0.66 (35593 hom., cov: 33)
• Consequence: SMARCAD1 NM_020159.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.275

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMARCAD1	NM_020159.5	c.705+2324G>C		intron_variant		ENST00000354268.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCAD1	ENST00000354268.9	c.705+2324G>C		intron_variant		1	NM_020159.5	P4

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100426 AN: 152008 Hom.: 35576 Cov.: 33

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.751

Gnomad AMR AF: 0.760

Gnomad ASJ AF: 0.774

Gnomad EAS AF: 0.893

Gnomad SAS AF: 0.820

Gnomad FIN AF: 0.778

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.681

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

GnomAD4 genome AF: 0.660 AC: 100461 AN: 152126 Hom.: 35593 Cov.: 33 AF XY: 0.666 AC XY: 49484 AN XY: 74344

Gnomad4 AFR AF: 0.376

Gnomad4 AMR AF: 0.760

Gnomad4 ASJ AF: 0.774

Gnomad4 EAS AF: 0.893

Gnomad4 SAS AF: 0.821

Gnomad4 FIN AF: 0.778

Gnomad4 NFE AF: 0.757

Gnomad4 OTH AF: 0.684

Alfa AF: 0.587 Hom.: 1917

Bravo AF: 0.647

Asia WGS AF: 0.822 AC: 2861 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.7
DANN	Benign	0.79

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: rs728989; hg19: chr4-95164481;