chr10-80494291-A-G

Variant names:

• chr10-80494291-A-G
• rs6586030
• NM_030927.4:c.81+4977A>G

Variant summary

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

The NM_030927.4(TSPAN14):​c.81+4977A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.886 in 152,296 control chromosomes in the GnomAD database, including 60,024 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 0.89 (60024 hom., cov: 34)
• Consequence: TSPAN14 NM_030927.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0250
• Publications: 40 publications found

Genes affected

TSPAN14 (HGNC:23303): (tetraspanin 14) Enables enzyme binding activity. Involved in positive regulation of Notch signaling pathway; protein localization to plasma membrane; and protein maturation. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPAN14	NM_030927.4	c.81+4977A>G		intron_variant	Intron 2 of 8	ENST00000429989.8	NP_112189.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSPAN14	ENST00000429989.8	c.81+4977A>G		intron_variant	Intron 2 of 8	1	NM_030927.4	ENSP00000396270.2

Frequencies

GnomAD3 genomes AF: 0.886 AC: 134782 AN: 152178 Hom.: 59968 Cov.: 34

Gnomad AFR AF: 0.959

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.906

Gnomad ASJ AF: 0.908

Gnomad EAS AF: 0.978

Gnomad SAS AF: 0.935

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.840

Gnomad OTH AF: 0.895

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

GnomAD4 genome AF: 0.886 AC: 134897 AN: 152296 Hom.: 60024 Cov.: 34 AF XY: 0.887 AC XY: 66028 AN XY: 74464

African (AFR) AF: 0.959 AC: 39881 AN: 41580

American (AMR) AF: 0.906 AC: 13869 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.908 AC: 3152 AN: 3472

East Asian (EAS) AF: 0.978 AC: 5067 AN: 5180

South Asian (SAS) AF: 0.934 AC: 4513 AN: 4830

European-Finnish (FIN) AF: 0.798 AC: 8453 AN: 10590

Middle Eastern (MID) AF: 0.918 AC: 270 AN: 294

European-Non Finnish (NFE) AF: 0.840 AC: 57115 AN: 68016

Other (OTH) AF: 0.895 AC: 1893 AN: 2114

Alfa AF: 0.859 Hom.: 101175

Bravo AF: 0.895

Asia WGS AF: 0.940 AC: 3267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.8
DANN	Benign	0.63
PhyloP100		0.025
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: rs6586030; hg19: chr10-82254047;