rs2117429

Variant names:

• chr4-153531800-C-G
• rs2117429
• NM_001131007.2:c.240-18273C>G

Variant summary

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

The NM_001131007.2(TMEM131L):​c.240-18273C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,046 control chromosomes in the GnomAD database, including 5,038 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 0.25 (5038 hom., cov: 32)
• Consequence: TMEM131L NM_001131007.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.536
• Publications: 3 publications found

Genes affected

TMEM131L (HGNC:29146): (transmembrane 131 like) Involved in negative regulation of canonical Wnt signaling pathway and negative regulation of immature T cell proliferation in thymus. Located in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

LOC105377498 (HGNC:):

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 (AMR) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM131L	NM_001131007.2	c.240-18273C>G		intron_variant	Intron 3 of 34	ENST00000409959.8	NP_001124479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM131L	ENST00000409959.8	c.240-18273C>G		intron_variant	Intron 3 of 34	5	NM_001131007.2	ENSP00000386787.3
TMEM131L	ENST00000409663.7	c.240-18273C>G		intron_variant	Intron 3 of 34	5		ENSP00000386574.3
TMEM131L	ENST00000445960.5	n.196-18273C>G		intron_variant	Intron 2 of 4	4		ENSP00000413054.1

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38663 AN: 151928 Hom.: 5026 Cov.: 32

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.255 AC: 38713 AN: 152046 Hom.: 5038 Cov.: 32 AF XY: 0.254 AC XY: 18912 AN XY: 74324

African (AFR) AF: 0.255 AC: 10550 AN: 41452

American (AMR) AF: 0.323 AC: 4934 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 900 AN: 3472

East Asian (EAS) AF: 0.313 AC: 1618 AN: 5176

South Asian (SAS) AF: 0.263 AC: 1268 AN: 4816

European-Finnish (FIN) AF: 0.252 AC: 2662 AN: 10560

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.234 AC: 15905 AN: 67976

Other (OTH) AF: 0.262 AC: 554 AN: 2112

Alfa AF: 0.229 Hom.: 512

Bravo AF: 0.264

Asia WGS AF: 0.296 AC: 1026 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	1.4
DANN	Benign	0.21
PhyloP100		-0.54
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: rs2117429; hg19: chr4-154452952;