rs11097407

Variant names:

• chr4-94224984-G-C
• rs11097407
• NM_020159.5:c.191-1135G>C

Your query was ambiguous. Multiple possible variants found:

• chr4-94224984-G-C
• chr4-94224984-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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]

SMARCAD1 Gene-Disease associations (from GenCC):

• ectodermal dysplasia syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: Illumina
• isolated congenital adermatoglyphia

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• palmoplantar keratoderma-sclerodactyly syndrome

  Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: G2P, Orphanet
• absence of fingerprints-congenital milia syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SMARCAD1	NM_020159.5	c.191-1135G>C		intron_variant	Intron 2 of 23	ENST00000354268.9	NP_064544.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCAD1	ENST00000354268.9	c.191-1135G>C		intron_variant	Intron 2 of 23	1	NM_020159.5	ENSP00000346217.4

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

African (AFR) AF: 0.224 AC: 9298 AN: 41464

American (AMR) AF: 0.423 AC: 6455 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 935 AN: 3472

East Asian (EAS) AF: 0.713 AC: 3680 AN: 5160

South Asian (SAS) AF: 0.522 AC: 2514 AN: 4816

European-Finnish (FIN) AF: 0.211 AC: 2233 AN: 10568

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.284 AC: 19328 AN: 67968

Other (OTH) AF: 0.303 AC: 641 AN: 2116

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
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11097407; hg19: chr4-95146135; COSMIC: COSV107445646;