rs728989

Variant names:

• chr4-94243330-G-C
• rs728989
• NM_020159.5:c.705+2324G>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The ENST00000354268.9(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 ENST00000354268.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.275
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000354268.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCAD1	NM_020159.5	MANE Select	c.705+2324G>C		intron	N/A	NP_064544.2
	SMARCAD1	NM_001128429.3		c.705+2324G>C		intron	N/A	NP_001121901.1
	SMARCAD1	NM_001128430.2		c.705+2324G>C		intron	N/A	NP_001121902.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCAD1	ENST00000354268.9	TSL:1 MANE Select	c.705+2324G>C		intron	N/A	ENSP00000346217.4
	SMARCAD1	ENST00000359052.8	TSL:1	c.705+2324G>C		intron	N/A	ENSP00000351947.4
	SMARCAD1	ENST00000457823.6	TSL:1	c.705+2324G>C		intron	N/A	ENSP00000415576.2

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

African (AFR) AF: 0.376 AC: 15593 AN: 41496

American (AMR) AF: 0.760 AC: 11628 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.774 AC: 2684 AN: 3468

East Asian (EAS) AF: 0.893 AC: 4609 AN: 5162

South Asian (SAS) AF: 0.821 AC: 3956 AN: 4818

European-Finnish (FIN) AF: 0.778 AC: 8226 AN: 10578

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.757 AC: 51446 AN: 67988

Other (OTH) AF: 0.684 AC: 1444 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.7
DANN	Benign	0.79
PhyloP100		-0.28
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: rs728989; hg19: chr4-95164481;