4-94208087-T-C

Position:

• chr4-94208087-T-C

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The ENST00000354268.9(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 ENST00000354268.9 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.938

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCAD1	NM_020159.5	c.-50+17T>C		intron_variant		ENST00000354268.9	NP_064544.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCAD1	ENST00000354268.9	c.-50+17T>C		intron_variant		1	NM_020159.5	ENSP00000346217	P4

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

GnomAD3 exomes AF: 0.649 AC: 84564 AN: 130224 Hom.: 28008 AF XY: 0.641 AC XY: 45514 AN XY: 71024

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 SAS exome AF: 0.635

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

Gnomad4 AFR exome AF: 0.908

Gnomad4 AMR exome AF: 0.745

Gnomad4 ASJ exome AF: 0.547

Gnomad4 EAS exome AF: 0.741

Gnomad4 SAS exome AF: 0.632

Gnomad4 FIN exome AF: 0.568

Gnomad4 NFE exome AF: 0.587

Gnomad4 OTH exome AF: 0.622

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

Gnomad4 AFR AF: 0.906

Gnomad4 AMR AF: 0.689

Gnomad4 ASJ AF: 0.556

Gnomad4 EAS AF: 0.719

Gnomad4 SAS AF: 0.640

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.590

Gnomad4 OTH AF: 0.654

Alfa AF: 0.610 Hom.: 10593

Bravo AF: 0.711

Asia WGS AF: 0.702 AC: 2442 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	20
DANN	Benign	0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs2276910; hg19: chr4-95129238;