14-50656877-C-T

Variant names:

• chr14-50656877-C-T
• rs923908
• NM_021818.4:c.535+8302G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021818.4(SAV1):​c.535+8302G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 151,946 control chromosomes in the GnomAD database, including 18,289 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.48 (18289 hom., cov: 31)
• Consequence: SAV1 NM_021818.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.23
• Publications: 6 publications found

Genes affected

SAV1 (HGNC:17795): (salvador family WW domain containing protein 1) WW domain-containing proteins are found in all eukaryotes and play an important role in the regulation of a wide variety of cellular functions such as protein degradation, transcription, and RNA splicing. This gene encodes a protein with two WW domains, a SARAH domain, and a coiled-coil region and is ubiquitously expressed in adult tissues. This protein binds to MST1 (mammalian sterile 20-like kinase 1) and promotes MST1-induced apoptosis. It has also been shown to bind to HAX1 (hematopoietic cell-specific protein 1 (HS1)-associated protein X-1) and to attenuate the anti-apoptotic effects of HAX1. Studies in human and mouse suggest this gene acts as a tumor suppressor. [provided by RefSeq, Aug 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAV1	NM_021818.4	c.535+8302G>A		intron_variant	Intron 2 of 4	ENST00000324679.5	NP_068590.1
SAV1	XM_011537057.4	c.436+8302G>A		intron_variant	Intron 3 of 5		XP_011535359.1
SAV1	XM_047431659.1	c.536-7488G>A		intron_variant	Intron 2 of 3		XP_047287615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAV1	ENST00000324679.5	c.535+8302G>A		intron_variant	Intron 2 of 4	1	NM_021818.4	ENSP00000324729.4
SAV1	ENST00000555720.5	c.331+8302G>A		intron_variant	Intron 1 of 4	1		ENSP00000451492.1
SAV1	ENST00000553731.1	c.187+8302G>A		intron_variant	Intron 1 of 1	5		ENSP00000450571.1

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72486 AN: 151828 Hom.: 18274 Cov.: 31

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.469

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.477 AC: 72527 AN: 151946 Hom.: 18289 Cov.: 31 AF XY: 0.482 AC XY: 35819 AN XY: 74244

African (AFR) AF: 0.313 AC: 12973 AN: 41422

American (AMR) AF: 0.587 AC: 8965 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 1718 AN: 3472

East Asian (EAS) AF: 0.726 AC: 3761 AN: 5184

South Asian (SAS) AF: 0.564 AC: 2715 AN: 4814

European-Finnish (FIN) AF: 0.553 AC: 5811 AN: 10514

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.514 AC: 34959 AN: 67956

Other (OTH) AF: 0.473 AC: 995 AN: 2102

Alfa AF: 0.496 Hom.: 53554

Bravo AF: 0.476

Asia WGS AF: 0.645 AC: 2244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.15
DANN	Benign	0.45
PhyloP100		-2.2
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: rs923908; hg19: chr14-51123595;