rs11097407

Positions:

• chr4-94224984-G-C
• chr4-94224984-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.191-1135G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,046 control chromosomes in the GnomAD database, including 7,748 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 0.30 (7748 hom., cov: 32)
• Consequence: SMARCAD1 NM_020159.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCAD1	NM_020159.5	c.191-1135G>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.191-1135G>C		intron_variant		1	NM_020159.5	ENSP00000346217	P4

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45396 AN: 151928 Hom.: 7722 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.290

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.714

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.299 AC: 45431 AN: 152046 Hom.: 7748 Cov.: 32 AF XY: 0.305 AC XY: 22664 AN XY: 74328

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.713

Gnomad4 SAS AF: 0.522

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.284

Gnomad4 OTH AF: 0.303

Alfa AF: 0.288 Hom.: 3946

Bravo AF: 0.313

Asia WGS AF: 0.601 AC: 2089 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.20
DANN	Benign	0.44

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: rs11097407; hg19: chr4-95146135;