4-94225904-C-G

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.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

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=-0.95).
• BP6: Variant 4-94225904-C-G is Benign according to our data. Variant chr4-94225904-C-G is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMARCAD1	NM_020159.5	c.191-215C>G		intron_variant		ENST00000354268.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCAD1	ENST00000354268.9	c.191-215C>G		intron_variant		1	NM_020159.5	P4

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

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.490

Gnomad4 ASJ AF: 0.384

Gnomad4 EAS AF: 0.715

Gnomad4 SAS AF: 0.588

Gnomad4 FIN AF: 0.386

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.390

Alfa AF: 0.254 Hom.: 597

Bravo AF: 0.403

Asia WGS AF: 0.633 AC: 2198 AN: 3472

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	-0.95
Cadd	Benign	0.66
Dann	Benign	0.36

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: rs2632401; hg19: chr4-95147055;