4-94226402-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_020159.5(SMARCAD1):c.368+106C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.034 (24 hom., cov: 18)
  • Exomes 𝑓: 0.038 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: SMARCAD1 NM_020159.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.31

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=-0.92).
• BP6: Variant 4-94226402-C-T is Benign according to our data. Variant chr4-94226402-C-T is described in ClinVar as [Benign]. Clinvar id is 1253074.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0345 (4217/122306) while in subpopulation AFR AF= 0.0481 (1548/32156). AF 95% confidence interval is 0.0461. There are 24 homozygotes in gnomad4. There are 2056 alleles in male gnomad4 subpopulation. Median coverage is 18. This position pass quality control queck.
• BS2: High AC in GnomAd at 4208 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMARCAD1	NM_020159.5	c.368+106C>T		intron_variant		ENST00000354268.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCAD1	ENST00000354268.9	c.368+106C>T		intron_variant		1	NM_020159.5	P4

Frequencies

GnomAD3 genomes AF: 0.0344 AC: 4208 AN: 122304 Hom.: 23 Cov.: 18

Gnomad AFR AF: 0.0480

Gnomad AMI AF: 0.0255

Gnomad AMR AF: 0.0216

Gnomad ASJ AF: 0.0440

Gnomad EAS AF: 0.0332

Gnomad SAS AF: 0.0168

Gnomad FIN AF: 0.0415

Gnomad MID AF: 0.0509

Gnomad NFE AF: 0.0300

Gnomad OTH AF: 0.0304

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0382 AC: 12673 AN: 331916 Hom.: 2 AF XY: 0.0388 AC XY: 6898 AN XY: 177740

Gnomad4 AFR exome AF: 0.0533

Gnomad4 AMR exome AF: 0.0442

Gnomad4 ASJ exome AF: 0.0491

Gnomad4 EAS exome AF: 0.0357

Gnomad4 SAS exome AF: 0.0454

Gnomad4 FIN exome AF: 0.0730

Gnomad4 NFE exome AF: 0.0327

Gnomad4 OTH exome AF: 0.0373

GnomAD4 genome AF: 0.0345 AC: 4217 AN: 122306 Hom.: 24 Cov.: 18 AF XY: 0.0359 AC XY: 2056 AN XY: 57296

Gnomad4 AFR AF: 0.0481

Gnomad4 AMR AF: 0.0217

Gnomad4 ASJ AF: 0.0440

Gnomad4 EAS AF: 0.0331

Gnomad4 SAS AF: 0.0169

Gnomad4 FIN AF: 0.0415

Gnomad4 NFE AF: 0.0300

Gnomad4 OTH AF: 0.0308

Alfa AF: 0.134 Hom.: 327

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

Jun 19, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.19
Dann	Benign	0.19

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

Publications

LitVar

Other links and lift over

dbSNP: rs72665660; hg19: chr4-95147553; COSMIC: COSV62773420;