chr4-94240845-C-T

Variant names:

• chr4-94240845-C-T
• rs2306803
• NM_020159.5:c.605-61C>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.605-61C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 1,270,548 control chromosomes in the GnomAD database, including 95,483 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (8729 hom., cov: 32)
  • Exomes 𝑓: 0.39 (86754 hom.)
• Consequence: SMARCAD1 NM_020159.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.743
• Publications: 3 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 4-94240845-C-T is Benign according to our data. Variant chr4-94240845-C-T is described in ClinVar as Benign. ClinVar VariationId is 1261751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.487 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.605-61C>T		intron	N/A	NP_064544.2	Q9H4L7-1
	SMARCAD1	NM_001128429.3		c.605-61C>T		intron	N/A	NP_001121901.1	Q9H4L7-2
	SMARCAD1	NM_001128430.2		c.605-61C>T		intron	N/A	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.605-61C>T		intron	N/A	ENSP00000346217.4	Q9H4L7-1
	SMARCAD1	ENST00000359052.8	TSL:1	c.605-61C>T		intron	N/A	ENSP00000351947.4	Q9H4L7-2
	SMARCAD1	ENST00000457823.6	TSL:1	c.605-61C>T		intron	N/A	ENSP00000415576.2	Q9H4L7-2

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47539 AN: 151818 Hom.: 8718 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.314

GnomAD4 exome AF: 0.389 AC: 434658 AN: 1118612 Hom.: 86754 AF XY: 0.393 AC XY: 223949 AN XY: 570040

African (AFR) AF: 0.112 AC: 2976 AN: 26622

American (AMR) AF: 0.365 AC: 15201 AN: 41694

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 9060 AN: 23664

East Asian (EAS) AF: 0.478 AC: 17593 AN: 36794

South Asian (SAS) AF: 0.479 AC: 36687 AN: 76632

European-Finnish (FIN) AF: 0.369 AC: 19012 AN: 51486

Middle Eastern (MID) AF: 0.339 AC: 1652 AN: 4870

European-Non Finnish (NFE) AF: 0.389 AC: 314339 AN: 808266

Other (OTH) AF: 0.373 AC: 18138 AN: 48584

GnomAD4 genome AF: 0.313 AC: 47554 AN: 151936 Hom.: 8729 Cov.: 32 AF XY: 0.316 AC XY: 23476 AN XY: 74238

African (AFR) AF: 0.119 AC: 4929 AN: 41440

American (AMR) AF: 0.328 AC: 5007 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1306 AN: 3472

East Asian (EAS) AF: 0.503 AC: 2599 AN: 5164

South Asian (SAS) AF: 0.487 AC: 2345 AN: 4816

European-Finnish (FIN) AF: 0.368 AC: 3879 AN: 10532

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.388 AC: 26330 AN: 67930

Other (OTH) AF: 0.322 AC: 679 AN: 2106

Alfa AF: 0.336 Hom.: 1199

Bravo AF: 0.302

Asia WGS AF: 0.469 AC: 1632 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	13
DANN	Benign	0.79
PhyloP100		-0.74
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2306803; hg19: chr4-95161996; COSMIC: COSV62773875;