rs8026

Variant names:

• chr4-94291034-A-G
• rs8026
• NM_020159.5:c.*1500A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020159.5(SMARCAD1):​c.*1500A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 437,872 control chromosomes in the GnomAD database, including 44,195 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 0.38 (11896 hom., cov: 32)
  • Exomes 𝑓: 0.46 (32299 hom.)
• Consequence: SMARCAD1 NM_020159.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05
• 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: Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• palmoplantar keratoderma-sclerodactyly syndrome

  Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, G2P
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020159.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCAD1	NM_020159.5	MANE Select	c.*1500A>G		3_prime_UTR	Exon 24 of 24	NP_064544.2	Q9H4L7-1
	SMARCAD1	NM_001128429.3		c.*1500A>G		3_prime_UTR	Exon 24 of 24	NP_001121901.1	Q9H4L7-2
	SMARCAD1	NM_001128430.2		c.*1500A>G		3_prime_UTR	Exon 24 of 24	NP_001121902.1	Q9H4L7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCAD1	ENST00000354268.9	TSL:1 MANE Select	c.*1500A>G		3_prime_UTR	Exon 24 of 24	ENSP00000346217.4	Q9H4L7-1
	SMARCAD1	ENST00000359052.8	TSL:1	c.*1500A>G		3_prime_UTR	Exon 24 of 24	ENSP00000351947.4	Q9H4L7-2
	SMARCAD1	ENST00000902279.1		c.*1500A>G		3_prime_UTR	Exon 24 of 24	ENSP00000572338.1

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57518 AN: 151836 Hom.: 11877 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.369

GnomAD2 exomes AF: 0.487 AC: 60105 AN: 123494 AF XY: 0.487

Gnomad AFR exome AF: 0.242

Gnomad AMR exome AF: 0.623

Gnomad ASJ exome AF: 0.397

Gnomad EAS exome AF: 0.707

Gnomad FIN exome AF: 0.387

Gnomad NFE exome AF: 0.403

Gnomad OTH exome AF: 0.437

GnomAD4 exome AF: 0.461 AC: 131684 AN: 285918 Hom.: 32299 Cov.: 0 AF XY: 0.469 AC XY: 76354 AN XY: 162660

African (AFR) AF: 0.242 AC: 1883 AN: 7784

American (AMR) AF: 0.625 AC: 15450 AN: 24726

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 3809 AN: 9770

East Asian (EAS) AF: 0.719 AC: 6561 AN: 9124

South Asian (SAS) AF: 0.570 AC: 31846 AN: 55830

European-Finnish (FIN) AF: 0.385 AC: 4698 AN: 12188

Middle Eastern (MID) AF: 0.356 AC: 369 AN: 1036

European-Non Finnish (NFE) AF: 0.403 AC: 61360 AN: 152192

Other (OTH) AF: 0.430 AC: 5708 AN: 13268

GnomAD4 genome AF: 0.379 AC: 57546 AN: 151954 Hom.: 11896 Cov.: 32 AF XY: 0.386 AC XY: 28684 AN XY: 74276

African (AFR) AF: 0.242 AC: 10057 AN: 41486

American (AMR) AF: 0.481 AC: 7338 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1318 AN: 3460

East Asian (EAS) AF: 0.714 AC: 3697 AN: 5178

South Asian (SAS) AF: 0.588 AC: 2836 AN: 4824

European-Finnish (FIN) AF: 0.385 AC: 4069 AN: 10558

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.397 AC: 26950 AN: 67882

Other (OTH) AF: 0.377 AC: 794 AN: 2108

Alfa AF: 0.393 Hom.: 16532

Bravo AF: 0.382

Asia WGS AF: 0.629 AC: 2185 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.2
DANN	Benign	0.65
PhyloP100		2.1
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: rs8026; hg19: chr4-95212185;