rs139380407

Variant names:

• chr10-29458226-GCTC-G
• rs139380407
• NM_021738.3:c.*18_*20delGAG

Your query was ambiguous. Multiple possible variants found:

• chr10-29458226-GCTC-G
• chr10-29458226-GCTC-GCTCCTC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_021738.3(SVIL):​c.*18_*20delGAG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,611,846 control chromosomes in the GnomAD database, including 11,805 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.095 (856 hom., cov: 31)
  • Exomes 𝑓: 0.12 (10949 hom.)
• Consequence: SVIL NM_021738.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.450
• Publications: 2 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 -10 ACMG points.

• BP6: Variant 10-29458226-GCTC-G is Benign according to our data. Variant chr10-29458226-GCTC-G is described in ClinVar as Benign. ClinVar VariationId is 1242800.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.13 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.*18_*20delGAG		3_prime_UTR	Exon 38 of 38	NP_068506.2	O95425-1
	SVIL	NM_001323599.2		c.*18_*20delGAG		3_prime_UTR	Exon 39 of 39	NP_001310528.1	A0A6I8PIX7
	SVIL	NM_001323600.1		c.*18_*20delGAG		3_prime_UTR	Exon 37 of 37	NP_001310529.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SVIL	ENST00000355867.9	TSL:1 MANE Select	c.*18_*20delGAG		3_prime_UTR	Exon 38 of 38	ENSP00000348128.4	O95425-1
	SVIL	ENST00000375400.7	TSL:1	c.*18_*20delGAG		3_prime_UTR	Exon 36 of 36	ENSP00000364549.3	O95425-2
	SVIL-AS1	ENST00000413405.7	TSL:1	n.212-28925_212-28923delCTC		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0948 AC: 14421 AN: 152158 Hom.: 857 Cov.: 31

Gnomad AFR AF: 0.0466

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.0848

Gnomad ASJ AF: 0.0504

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0292

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.0875

GnomAD2 exomes AF: 0.0886 AC: 22164 AN: 250134 AF XY: 0.0883

Gnomad AFR exome AF: 0.0466

Gnomad AMR exome AF: 0.0457

Gnomad ASJ exome AF: 0.0555

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.151

Gnomad NFE exome AF: 0.128

Gnomad OTH exome AF: 0.0917

GnomAD4 exome AF: 0.116 AC: 168882 AN: 1459570 Hom.: 10949 AF XY: 0.113 AC XY: 82210 AN XY: 726226

African (AFR) AF: 0.0454 AC: 1516 AN: 33410

American (AMR) AF: 0.0484 AC: 2154 AN: 44538

Ashkenazi Jewish (ASJ) AF: 0.0547 AC: 1427 AN: 26090

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39660

South Asian (SAS) AF: 0.0316 AC: 2725 AN: 86124

European-Finnish (FIN) AF: 0.153 AC: 8148 AN: 53398

Middle Eastern (MID) AF: 0.0456 AC: 260 AN: 5706

European-Non Finnish (NFE) AF: 0.132 AC: 146455 AN: 1110356

Other (OTH) AF: 0.103 AC: 6188 AN: 60288

GnomAD4 genome AF: 0.0947 AC: 14418 AN: 152276 Hom.: 856 Cov.: 31 AF XY: 0.0953 AC XY: 7093 AN XY: 74446

African (AFR) AF: 0.0465 AC: 1932 AN: 41580

American (AMR) AF: 0.0847 AC: 1295 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0504 AC: 175 AN: 3470

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5186

South Asian (SAS) AF: 0.0290 AC: 140 AN: 4824

European-Finnish (FIN) AF: 0.145 AC: 1535 AN: 10596

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 8989 AN: 68002

Other (OTH) AF: 0.0866 AC: 183 AN: 2114

Alfa AF: 0.106 Hom.: 166

Bravo AF: 0.0881

Asia WGS AF: 0.0190 AC: 68 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.45
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: rs139380407; hg19: chr10-29747155; COSMIC: COSV63443923;