2-112100065-A-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM87B	NM_032824.3	c.1377-557A>G		intron_variant	Intron 14 of 18	ENST00000283206.9	NP_116213.1
TMEM87B	NM_001329914.2	c.1377-557A>G		intron_variant	Intron 14 of 18		NP_001316843.1
TMEM87B	XM_005263827.3	c.1374-557A>G		intron_variant	Intron 14 of 18		XP_005263884.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM87B	ENST00000283206.9	c.1377-557A>G		intron_variant	Intron 14 of 18	2	NM_032824.3	ENSP00000283206.4
TMEM87B	ENST00000650799.2	c.1377-557A>G		intron_variant	Intron 14 of 18			ENSP00000498298.2
TMEM87B	ENST00000452614.6	c.1326-557A>G		intron_variant	Intron 13 of 17	1		ENSP00000393998.2
TMEM87B	ENST00000649734.1	c.249-557A>G		intron_variant	Intron 4 of 8			ENSP00000498041.1
TMEM87B	ENST00000471632.1	c.327+2774A>G		intron_variant	Intron 4 of 4	3		ENSP00000516030.1

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

Gnomad4 AFR AF: 0.486

Gnomad4 AMR AF: 0.507

Gnomad4 ASJ AF: 0.517

Gnomad4 EAS AF: 0.870

Gnomad4 SAS AF: 0.396

Gnomad4 FIN AF: 0.381

Gnomad4 NFE AF: 0.493

Gnomad4 OTH AF: 0.537

Alfa AF: 0.509 Hom.: 33122

Bravo AF: 0.507

Asia WGS AF: 0.658 AC: 2287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.016
DANN	Benign	0.68

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: rs9653422; hg19: chr2-112857642;