4-94240845-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:1
• Conservation: PhyloP100: -0.743

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 -14 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 id is 1261751.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMARCAD1	NM_020159.5	c.605-61C>T		intron_variant		ENST00000354268.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCAD1	ENST00000354268.9	c.605-61C>T		intron_variant		1	NM_020159.5	P4

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

Gnomad4 AFR exome AF: 0.112

Gnomad4 AMR exome AF: 0.365

Gnomad4 ASJ exome AF: 0.383

Gnomad4 EAS exome AF: 0.478

Gnomad4 SAS exome AF: 0.479

Gnomad4 FIN exome AF: 0.369

Gnomad4 NFE exome AF: 0.389

Gnomad4 OTH exome AF: 0.373

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

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.376

Gnomad4 EAS AF: 0.503

Gnomad4 SAS AF: 0.487

Gnomad4 FIN AF: 0.368

Gnomad4 NFE AF: 0.388

Gnomad4 OTH AF: 0.322

Alfa AF: 0.336 Hom.: 1199

Bravo AF: 0.302

Asia WGS AF: 0.469 AC: 1632 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	13
Dann	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs2306803; hg19: chr4-95161996; COSMIC: COSV62773875;