rs7289126

Positions:

• chr22-38232300-C-A
• chr22-38232300-C-T

Variant summary

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

The NM_012264.5(TMEM184B):​c.359-966G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 152,074 control chromosomes in the GnomAD database, including 27,381 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 0.58 (27377 hom., cov: 31)
  • Exomes 𝑓: 0.59 (4 hom.)
• Consequence: TMEM184B NM_012264.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.150

Genes affected

TMEM184B (HGNC:1310): (transmembrane protein 184B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM184B	NM_012264.5	c.359-966G>T		intron_variant		ENST00000361906.8	NP_036396.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM184B	ENST00000361906.8	c.359-966G>T		intron_variant		1	NM_012264.5	ENSP00000355210	P1

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87881 AN: 151934 Hom.: 27310 Cov.: 31

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.546

GnomAD4 exome AF: 0.591 AC: 13 AN: 22 Hom.: 4 AF XY: 0.500 AC XY: 6 AN XY: 12

Gnomad4 AMR exome AF: 0.500

Gnomad4 FIN exome AF: 0.625

Gnomad4 NFE exome AF: 0.583

GnomAD4 genome AF: 0.579 AC: 88015 AN: 152052 Hom.: 27377 Cov.: 31 AF XY: 0.580 AC XY: 43069 AN XY: 74304

Gnomad4 AFR AF: 0.821

Gnomad4 AMR AF: 0.532

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.456

Gnomad4 SAS AF: 0.629

Gnomad4 FIN AF: 0.470

Gnomad4 NFE AF: 0.470

Gnomad4 OTH AF: 0.549

Alfa AF: 0.491 Hom.: 39281

Bravo AF: 0.589

Asia WGS AF: 0.607 AC: 2116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.86

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: rs7289126; hg19: chr22-38628306;