rs183993

Variant names:

• chr4-94208874-G-A
• rs183993
• NM_020159.5:c.190+290G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-94208874-G-A
• chr4-94208874-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020159.5(SMARCAD1):​c.190+290G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 152,020 control chromosomes in the GnomAD database, including 23,356 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.55 (23356 hom., cov: 31)
• Consequence: SMARCAD1 NM_020159.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.526
• Publications: 9 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 4-94208874-G-A is Benign according to our data. Variant chr4-94208874-G-A is described in ClinVar as Benign. ClinVar VariationId is 1243509.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
SMARCAD1	NM_020159.5	c.190+290G>A		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.190+290G>A		intron_variant	Intron 2 of 23	1	NM_020159.5	ENSP00000346217.4

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83286 AN: 151902 Hom.: 23342 Cov.: 31

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.548 AC: 83342 AN: 152020 Hom.: 23356 Cov.: 31 AF XY: 0.554 AC XY: 41171 AN XY: 74302

African (AFR) AF: 0.417 AC: 17276 AN: 41436

American (AMR) AF: 0.632 AC: 9663 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 1847 AN: 3472

East Asian (EAS) AF: 0.718 AC: 3713 AN: 5170

South Asian (SAS) AF: 0.636 AC: 3065 AN: 4820

European-Finnish (FIN) AF: 0.572 AC: 6052 AN: 10574

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.586 AC: 39829 AN: 67950

Other (OTH) AF: 0.551 AC: 1162 AN: 2110

Alfa AF: 0.576 Hom.: 9638

Bravo AF: 0.553

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.1
DANN	Benign	0.74
PhyloP100		0.53
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: rs183993; hg19: chr4-95130025;