rs2587708

Positions:

• chr2-119435261-G-A
• chr2-119435261-G-C

Variant summary

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

The NM_183240.3(TMEM37):​c.22-1628G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 141,832 control chromosomes in the GnomAD database, including 37,619 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 0.75 (37619 hom., cov: 32)
• Consequence: TMEM37 NM_183240.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.908

Genes affected

TMEM37 (HGNC:18216): (transmembrane protein 37) Predicted to enable calcium channel activity and voltage-gated ion channel activity. Predicted to be involved in calcium ion transmembrane transport and regulation of ion transmembrane transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM37 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM37	NM_183240.3	c.22-1628G>A		intron_variant		ENST00000306406.5	NP_899063.2
TMEM37	XM_011510659.3	c.58-1628G>A		intron_variant			XP_011508961.1
TMEM37	XM_006712300.4	c.-240-1628G>A		intron_variant			XP_006712363.1
TMEM37	XM_047443445.1	c.-240-1628G>A		intron_variant			XP_047299401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM37	ENST00000306406.5	c.22-1628G>A		intron_variant		1	NM_183240.3	ENSP00000303148.4
TMEM37	ENST00000409826.1	c.58-1628G>A		intron_variant		3		ENSP00000387015.1
TMEM37	ENST00000417645.1	c.39-1628G>A		intron_variant		3		ENSP00000400770.1
TMEM37	ENST00000465296.1	n.162-1628G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.752 AC: 106541 AN: 141716 Hom.: 37557 Cov.: 32

Gnomad AFR AF: 0.793

Gnomad AMI AF: 0.837

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.773

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.743

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

GnomAD4 genome AF: 0.752 AC: 106663 AN: 141832 Hom.: 37619 Cov.: 32 AF XY: 0.747 AC XY: 51635 AN XY: 69108

Gnomad4 AFR AF: 0.794

Gnomad4 AMR AF: 0.748

Gnomad4 ASJ AF: 0.773

Gnomad4 EAS AF: 0.690

Gnomad4 SAS AF: 0.662

Gnomad4 FIN AF: 0.692

Gnomad4 NFE AF: 0.743

Gnomad4 OTH AF: 0.743

Alfa AF: 0.781 Hom.: 15454

Bravo AF: 0.713

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.23
DANN	Benign	0.51

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: rs2587708; hg19: chr2-120192837;