rs1425118

Positions:

• chr2-216094176-C-G
• chr2-216094176-C-T

Variant summary

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

The ENST00000437356.7(TMEM169):​c.-126-1662C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,018 control chromosomes in the GnomAD database, including 2,935 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 0.19 (2935 hom., cov: 32)
• Consequence: TMEM169 ENST00000437356.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.359

Genes affected

TMEM169 (HGNC:25130): (transmembrane protein 169) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM169	NM_001142311.2	c.-126-1662C>G		intron_variant		ENST00000437356.7	NP_001135783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM169	ENST00000437356.7	c.-126-1662C>G		intron_variant		1	NM_001142311.2	ENSP00000401305	P1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29484 AN: 151900 Hom.: 2935 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.194 AC: 29498 AN: 152018 Hom.: 2935 Cov.: 32 AF XY: 0.193 AC XY: 14345 AN XY: 74306

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.255

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.198

Alfa AF: 0.0970 Hom.: 150

Bravo AF: 0.192

Asia WGS AF: 0.200 AC: 694 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.75

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: rs1425118; hg19: chr2-216958899;