rs2117429

Positions:

• chr4-153531800-C-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TMEM131L	NM_001131007.2	c.240-18273C>G		intron_variant		ENST00000409959.8
LOC105377498	XR_939363.3	n.174-3707G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM131L	ENST00000409959.8	c.240-18273C>G		intron_variant		5	NM_001131007.2	A2
TMEM131L	ENST00000409663.7	c.240-18273C>G		intron_variant		5		P4
TMEM131L	ENST00000445960.5	c.196-18273C>G		intron_variant, NMD_transcript_variant		4

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

Gnomad4 AFR AF: 0.255

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.313

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.262

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

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: rs2117429; hg19: chr4-154452952;