NM_020159.5:c.-50+17T>C

Variant names:

• chr4-94208087-T-C
• rs2276910
• NM_020159.5:c.-50+17T>C

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_020159.5(SMARCAD1):​c.-50+17T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 520,662 control chromosomes in the GnomAD database, including 110,642 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.69 (37686 hom., cov: 30)
  • Exomes 𝑓: 0.62 (72956 hom.)
• Consequence: SMARCAD1 NM_020159.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.938
• Publications: 8 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: Orphanet, G2P
• absence of fingerprints-congenital milia syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 4-94208087-T-C is Benign according to our data. Variant chr4-94208087-T-C is described in ClinVar as Benign. ClinVar VariationId is 1225197.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.898 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.-50+17T>C		intron	N/A	NP_064544.2	Q9H4L7-1
	SMARCAD1	NM_001128429.3		c.-50+17T>C		intron	N/A	NP_001121901.1	Q9H4L7-2
	SMARCAD1	NM_001128430.2		c.-49-259T>C		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.-50+17T>C		intron	N/A	ENSP00000346217.4	Q9H4L7-1
	SMARCAD1	ENST00000359052.8	TSL:1	c.-49-259T>C		intron	N/A	ENSP00000351947.4	Q9H4L7-2
	SMARCAD1	ENST00000457823.6	TSL:1	c.-50+17T>C		intron	N/A	ENSP00000415576.2	Q9H4L7-2

Frequencies

GnomAD3 genomes AF: 0.691 AC: 104815 AN: 151632 Hom.: 37631 Cov.: 30

Gnomad AFR AF: 0.906

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.688

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.649

GnomAD2 exomes AF: 0.649 AC: 84564 AN: 130224 AF XY: 0.641

Gnomad AFR exome AF: 0.913

Gnomad AMR exome AF: 0.746

Gnomad ASJ exome AF: 0.553

Gnomad EAS exome AF: 0.708

Gnomad FIN exome AF: 0.563

Gnomad NFE exome AF: 0.591

Gnomad OTH exome AF: 0.608

GnomAD4 exome AF: 0.623 AC: 229672 AN: 368912 Hom.: 72956 Cov.: 2 AF XY: 0.619 AC XY: 127312 AN XY: 205522

African (AFR) AF: 0.908 AC: 10177 AN: 11210

American (AMR) AF: 0.745 AC: 21695 AN: 29134

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 7655 AN: 13986

East Asian (EAS) AF: 0.741 AC: 11040 AN: 14900

South Asian (SAS) AF: 0.632 AC: 38099 AN: 60242

European-Finnish (FIN) AF: 0.568 AC: 8701 AN: 15310

Middle Eastern (MID) AF: 0.583 AC: 923 AN: 1582

European-Non Finnish (NFE) AF: 0.587 AC: 119572 AN: 203568

Other (OTH) AF: 0.622 AC: 11810 AN: 18980

GnomAD4 genome AF: 0.691 AC: 104933 AN: 151750 Hom.: 37686 Cov.: 30 AF XY: 0.692 AC XY: 51322 AN XY: 74116

African (AFR) AF: 0.906 AC: 37533 AN: 41432

American (AMR) AF: 0.689 AC: 10514 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 1928 AN: 3468

East Asian (EAS) AF: 0.719 AC: 3677 AN: 5112

South Asian (SAS) AF: 0.640 AC: 3057 AN: 4774

European-Finnish (FIN) AF: 0.574 AC: 6017 AN: 10484

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.590 AC: 40078 AN: 67900

Other (OTH) AF: 0.654 AC: 1382 AN: 2112

Alfa AF: 0.609 Hom.: 16308

Bravo AF: 0.711

Asia WGS AF: 0.702 AC: 2442 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.43
CADD	Benign	20
DANN	Benign	0.92
PhyloP100		0.94
PromoterAI		-0.14	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs2276910; hg19: chr4-95129238;