rs12150474

Positions:

• chr17-74239326-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032646.6(TTYH2):​c.635+1812G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0892 in 152,272 control chromosomes in the GnomAD database, including 795 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 0.089 (795 hom., cov: 32)
• Consequence: TTYH2 NM_032646.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.911

Genes affected

TTYH2 (HGNC:13877): (tweety family member 2) This gene encodes a member of the tweety family of proteins. Members of this family function as chloride anion channels. The encoded protein functions as a calcium(2+)-activated large conductance chloride(-) channel, and may play a role in kidney tumorigenesis. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTYH2	NM_032646.6	c.635+1812G>A		intron_variant		ENST00000269346.9	NP_116035.5
TTYH2	NM_001330453.2	c.572+1812G>A		intron_variant			NP_001317382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTYH2	ENST00000269346.9	c.635+1812G>A		intron_variant		1	NM_032646.6	ENSP00000269346	P1
TTYH2	ENST00000529107.5	c.572+1812G>A		intron_variant		2		ENSP00000433089
TTYH2	ENST00000578825.5	n.347+1812G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0892 AC: 13578 AN: 152154 Hom.: 794 Cov.: 32

Gnomad AFR AF: 0.0250

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0917

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0510

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.0892 AC: 13577 AN: 152272 Hom.: 795 Cov.: 32 AF XY: 0.0888 AC XY: 6613 AN XY: 74460

Gnomad4 AFR AF: 0.0249

Gnomad4 AMR AF: 0.0917

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0506

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.116

Alfa AF: 0.100 Hom.: 145

Bravo AF: 0.0821

Asia WGS AF: 0.0280 AC: 97 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.9
DANN	Benign	0.61

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: rs12150474; hg19: chr17-72235465;