2-112100065-A-G

Variant names:

• chr2-112100065-A-G
• rs9653422
• NM_032824.3:c.1377-557A>G

Variant summary

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

The NM_032824.3(TMEM87B):​c.1377-557A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 152,020 control chromosomes in the GnomAD database, including 19,228 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 0.50 (19228 hom., cov: 32)
• Consequence: TMEM87B NM_032824.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.889
• Publications: 8 publications found

Genes affected

TMEM87B (HGNC:25913): (transmembrane protein 87B) This gene encodes a protein that may interact with human papillomavirus type 18 E6 oncogene. The protein is also likely to be involved in endosome-to-trans-Golgi network retrograde transport. The gene is expressed in adult and fetal tissues, including brain and heart. This gene is a component of the 2q13 deletion syndrome. Mutations in this gene may be associated with congenital heart defects. [provided by RefSeq, Aug 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032824.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM87B	NM_032824.3	MANE Select	c.1377-557A>G		intron	N/A	NP_116213.1
	TMEM87B	NM_001329914.2		c.1377-557A>G		intron	N/A	NP_001316843.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM87B	ENST00000283206.9	TSL:2 MANE Select	c.1377-557A>G		intron	N/A	ENSP00000283206.4
	TMEM87B	ENST00000650799.2		c.1377-557A>G		intron	N/A	ENSP00000498298.2
	TMEM87B	ENST00000452614.6	TSL:1	c.1326-557A>G		intron	N/A	ENSP00000393998.2

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75383 AN: 151902 Hom.: 19212 Cov.: 32

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.870

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.496 AC: 75429 AN: 152020 Hom.: 19228 Cov.: 32 AF XY: 0.494 AC XY: 36673 AN XY: 74308

African (AFR) AF: 0.486 AC: 20143 AN: 41456

American (AMR) AF: 0.507 AC: 7749 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 1794 AN: 3468

East Asian (EAS) AF: 0.870 AC: 4504 AN: 5178

South Asian (SAS) AF: 0.396 AC: 1914 AN: 4828

European-Finnish (FIN) AF: 0.381 AC: 4016 AN: 10538

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.493 AC: 33505 AN: 67960

Other (OTH) AF: 0.537 AC: 1136 AN: 2114

Alfa AF: 0.504 Hom.: 53833

Bravo AF: 0.507

Asia WGS AF: 0.658 AC: 2287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.016
DANN	Benign	0.68
PhyloP100		-0.89
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: rs9653422; hg19: chr2-112857642;