chr4-153485526-A-G

Variant names:

• chr4-153485526-A-G
• rs17379636
• NM_001131007.2:c.239+11638A>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.239+11638A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 151,976 control chromosomes in the GnomAD database, including 19,568 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 0.49 (19568 hom., cov: 32)
• Consequence: TMEM131L NM_001131007.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42
• Publications: 4 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001131007.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM131L	NM_001131007.2	MANE Select	c.239+11638A>G		intron	N/A	NP_001124479.1	A2VDJ0-5
	TMEM131L	NM_015196.4		c.239+11638A>G		intron	N/A	NP_056011.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM131L	ENST00000409959.8	TSL:5 MANE Select	c.239+11638A>G		intron	N/A	ENSP00000386787.3	A2VDJ0-5
	TMEM131L	ENST00000409663.7	TSL:5	c.239+11638A>G		intron	N/A	ENSP00000386574.3	A2VDJ0-1
	TMEM131L	ENST00000886543.1		c.239+11638A>G		intron	N/A	ENSP00000556606.1

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74877 AN: 151858 Hom.: 19544 Cov.: 32

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.476

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

GnomAD4 genome AF: 0.493 AC: 74948 AN: 151976 Hom.: 19568 Cov.: 32 AF XY: 0.496 AC XY: 36857 AN XY: 74268

African (AFR) AF: 0.678 AC: 28078 AN: 41428

American (AMR) AF: 0.474 AC: 7239 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1343 AN: 3468

East Asian (EAS) AF: 0.587 AC: 3028 AN: 5160

South Asian (SAS) AF: 0.571 AC: 2753 AN: 4822

European-Finnish (FIN) AF: 0.419 AC: 4430 AN: 10566

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.391 AC: 26550 AN: 67952

Other (OTH) AF: 0.475 AC: 1003 AN: 2110

Alfa AF: 0.433 Hom.: 10211

Bravo AF: 0.506

Asia WGS AF: 0.623 AC: 2163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	14
DANN	Benign	0.80
PhyloP100		1.4
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: rs17379636; hg19: chr4-154406678;