rs2274494

Variant names:

• chr10-29471280-C-T
• rs2274494
• NM_021738.3:c.5530-37G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-29471280-C-T
• chr10-29471280-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_021738.3(SVIL):​c.5530-37G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 1,527,722 control chromosomes in the GnomAD database, including 109,941 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (11732 hom., cov: 32)
  • Exomes 𝑓: 0.37 (98209 hom.)
• Consequence: SVIL NM_021738.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.86
• Publications: 8 publications found

Genes affected

SVIL (HGNC:11480): (supervillin) This gene encodes a bipartite protein with distinct amino- and carboxy-terminal domains. The amino-terminus contains nuclear localization signals and the carboxy-terminus contains numerous consecutive sequences with extensive similarity to proteins in the gelsolin family of actin-binding proteins, which cap, nucleate, and/or sever actin filaments. The gene product is tightly associated with both actin filaments and plasma membranes, suggesting a role as a high-affinity link between the actin cytoskeleton and the membrane. The encoded protein appears to aid in both myosin II assembly during cell spreading and disassembly of focal adhesions. Several transcript variants encoding different isoforms of supervillin have been described. [provided by RefSeq, Apr 2016]

SVIL-AS1 (HGNC:):

SVIL-AS1 (HGNC:51219): (SVIL antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 10-29471280-C-T is Benign according to our data. Variant chr10-29471280-C-T is described in ClinVar as Benign. ClinVar VariationId is 1222618.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021738.3. 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
	SVIL	NM_021738.3	MANE Select	c.5530-37G>A		intron	N/A	NP_068506.2	O95425-1
	SVIL	NM_001323599.2		c.4600-37G>A		intron	N/A	NP_001310528.1	A0A6I8PIX7
	SVIL	NM_001323600.1		c.4348-37G>A		intron	N/A	NP_001310529.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SVIL	ENST00000355867.9	TSL:1 MANE Select	c.5530-37G>A		intron	N/A	ENSP00000348128.4	O95425-1
	SVIL	ENST00000375400.7	TSL:1	c.4252-37G>A		intron	N/A	ENSP00000364549.3	O95425-2
	SVIL-AS1	ENST00000413405.7	TSL:1	n.212-15875C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58843 AN: 151784 Hom.: 11706 Cov.: 32

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.352

GnomAD2 exomes AF: 0.418 AC: 84331 AN: 201848 AF XY: 0.412

Gnomad AFR exome AF: 0.409

Gnomad AMR exome AF: 0.516

Gnomad ASJ exome AF: 0.252

Gnomad EAS exome AF: 0.555

Gnomad FIN exome AF: 0.495

Gnomad NFE exome AF: 0.367

Gnomad OTH exome AF: 0.394

GnomAD4 exome AF: 0.375 AC: 515548 AN: 1375820 Hom.: 98209 Cov.: 21 AF XY: 0.375 AC XY: 254088 AN XY: 678420

African (AFR) AF: 0.389 AC: 11960 AN: 30714

American (AMR) AF: 0.500 AC: 18642 AN: 37318

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 5631 AN: 23830

East Asian (EAS) AF: 0.533 AC: 20157 AN: 37830

South Asian (SAS) AF: 0.394 AC: 31280 AN: 79388

European-Finnish (FIN) AF: 0.482 AC: 24970 AN: 51756

Middle Eastern (MID) AF: 0.285 AC: 1554 AN: 5448

European-Non Finnish (NFE) AF: 0.361 AC: 380175 AN: 1052762

Other (OTH) AF: 0.373 AC: 21179 AN: 56774

GnomAD4 genome AF: 0.388 AC: 58923 AN: 151902 Hom.: 11732 Cov.: 32 AF XY: 0.397 AC XY: 29497 AN XY: 74222

African (AFR) AF: 0.395 AC: 16364 AN: 41400

American (AMR) AF: 0.430 AC: 6561 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 796 AN: 3468

East Asian (EAS) AF: 0.536 AC: 2766 AN: 5156

South Asian (SAS) AF: 0.396 AC: 1902 AN: 4806

European-Finnish (FIN) AF: 0.484 AC: 5093 AN: 10518

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.359 AC: 24371 AN: 67968

Other (OTH) AF: 0.355 AC: 750 AN: 2110

Alfa AF: 0.359 Hom.: 3042

Bravo AF: 0.386

Asia WGS AF: 0.442 AC: 1534 AN: 3478

ClinVar

ClinVar submissions

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	-0.92
CADD	Benign	0.30
DANN	Benign	0.50
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2274494; hg19: chr10-29760209; COSMIC: COSV63446670; COSMIC: COSV63446670;