9-35829034-G-A

Variant names:

• chr9-35829034-G-A
• rs879284
• ENST00000377996.5:c.-450-12100G>A

Variant summary

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

The ENST00000377996.5(TMEM8B):​c.-450-12100G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 151,948 control chromosomes in the GnomAD database, including 3,577 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 0.21 (3577 hom., cov: 30)
• Consequence: TMEM8B ENST00000377996.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.35
• Publications: 7 publications found

Genes affected

TMEM8B (HGNC:21427): (transmembrane protein 8B) Involved in cell-matrix adhesion. Located in cell surface 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=-0.61).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000377996.5. 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
	TMEM8B	NM_001042590.4	MANE Select	c.-414G>A		upstream_gene	N/A	NP_001036055.2
	TMEM8B	NM_001363620.1		c.-414G>A		upstream_gene	N/A	NP_001350549.1
	TMEM8B	NM_001042589.3		c.-1213G>A		upstream_gene	N/A	NP_001036054.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM8B	ENST00000377996.5	TSL:2	c.-450-12100G>A		intron	N/A	ENSP00000367235.1
	TMEM8B	ENST00000643932.2	MANE Select	c.-414G>A		upstream_gene	N/A	ENSP00000493496.1
	TMEM8B	ENST00000377991.9	TSL:1	c.-1213G>A		upstream_gene	N/A	ENSP00000367230.4

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31876 AN: 151830 Hom.: 3574 Cov.: 30

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.210 AC: 31881 AN: 151948 Hom.: 3577 Cov.: 30 AF XY: 0.210 AC XY: 15581 AN XY: 74266

African (AFR) AF: 0.235 AC: 9721 AN: 41426

American (AMR) AF: 0.218 AC: 3334 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 939 AN: 3470

East Asian (EAS) AF: 0.369 AC: 1893 AN: 5130

South Asian (SAS) AF: 0.174 AC: 833 AN: 4794

European-Finnish (FIN) AF: 0.156 AC: 1650 AN: 10598

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12881 AN: 67942

Other (OTH) AF: 0.213 AC: 449 AN: 2108

Alfa AF: 0.199 Hom.: 1512

Bravo AF: 0.221

Asia WGS AF: 0.263 AC: 913 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	14
DANN	Benign	0.92
PhyloP100		2.4
PromoterAI		-0.021	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs879284; hg19: chr9-35829031; COSMIC: COSV65073989; COSMIC: COSV65073989;