NM_020159.5:c.191-215C>G

Variant names:

• chr4-94225904-C-G
• rs2632401
• NM_020159.5:c.191-215C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020159.5(SMARCAD1):​c.191-215C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 151,976 control chromosomes in the GnomAD database, including 12,702 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.40 (12702 hom., cov: 32)
• Consequence: SMARCAD1 NM_020159.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.415
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 4-94225904-C-G is Benign according to our data. Variant chr4-94225904-C-G is described in ClinVar as Benign. ClinVar VariationId is 1287784.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.696 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.191-215C>G		intron	N/A	NP_064544.2	Q9H4L7-1
	SMARCAD1	NM_001128429.3		c.191-215C>G		intron	N/A	NP_001121901.1	Q9H4L7-2
	SMARCAD1	NM_001128430.2		c.191-215C>G		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.191-215C>G		intron	N/A	ENSP00000346217.4	Q9H4L7-1
	SMARCAD1	ENST00000359052.8	TSL:1	c.191-215C>G		intron	N/A	ENSP00000351947.4	Q9H4L7-2
	SMARCAD1	ENST00000457823.6	TSL:1	c.191-215C>G		intron	N/A	ENSP00000415576.2	Q9H4L7-2

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60413 AN: 151858 Hom.: 12679 Cov.: 32

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.383

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

GnomAD4 genome AF: 0.398 AC: 60453 AN: 151976 Hom.: 12702 Cov.: 32 AF XY: 0.405 AC XY: 30058 AN XY: 74286

African (AFR) AF: 0.304 AC: 12590 AN: 41432

American (AMR) AF: 0.490 AC: 7485 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1328 AN: 3462

East Asian (EAS) AF: 0.715 AC: 3697 AN: 5172

South Asian (SAS) AF: 0.588 AC: 2836 AN: 4822

European-Finnish (FIN) AF: 0.386 AC: 4072 AN: 10562

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.399 AC: 27133 AN: 67940

Other (OTH) AF: 0.390 AC: 826 AN: 2116

Alfa AF: 0.254 Hom.: 597

Bravo AF: 0.403

Asia WGS AF: 0.633 AC: 2198 AN: 3472

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.66
DANN	Benign	0.36
PhyloP100		-0.41
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: rs2632401; hg19: chr4-95147055; COSMIC: COSV107445647;