22-38219529-A-T

Variant names:

• chr22-38219529-A-T
• rs1059804
• ENST00000436674.5:n.*3046T>A

Variant summary

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

The ENST00000436674.5(TMEM184B):​n.*3046T>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 874,882 control chromosomes in the GnomAD database, including 194,548 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 (41825 hom., cov: 29)
  • Exomes 𝑓: 0.70 (152723 hom.)
• Consequence: TMEM184B ENST00000436674.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0790
• Publications: 7 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM184B	NM_012264.5	c.*1940T>A		3_prime_UTR_variant	Exon 9 of 9	ENST00000361906.8	NP_036396.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM184B	ENST00000361906.8	c.*1940T>A		3_prime_UTR_variant	Exon 9 of 9	1	NM_012264.5	ENSP00000355210.3

Frequencies

GnomAD3 genomes AF: 0.747 AC: 111874 AN: 149826 Hom.: 41795 Cov.: 29

Gnomad AFR AF: 0.808

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.711

Gnomad EAS AF: 0.736

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.760

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.722

Gnomad OTH AF: 0.731

GnomAD4 exome AF: 0.696 AC: 504785 AN: 724966 Hom.: 152723 Cov.: 48 AF XY: 0.697 AC XY: 233228 AN XY: 334716

African (AFR) AF: 0.747 AC: 10266 AN: 13734

American (AMR) AF: 0.715 AC: 621 AN: 868

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 3120 AN: 4502

East Asian (EAS) AF: 0.709 AC: 2195 AN: 3094

South Asian (SAS) AF: 0.661 AC: 9237 AN: 13974

European-Finnish (FIN) AF: 0.733 AC: 456 AN: 622

Middle Eastern (MID) AF: 0.697 AC: 990 AN: 1420

European-Non Finnish (NFE) AF: 0.696 AC: 461478 AN: 663124

Other (OTH) AF: 0.695 AC: 16422 AN: 23628

GnomAD4 genome AF: 0.747 AC: 111950 AN: 149916 Hom.: 41825 Cov.: 29 AF XY: 0.746 AC XY: 54539 AN XY: 73152

African (AFR) AF: 0.808 AC: 32935 AN: 40774

American (AMR) AF: 0.742 AC: 11205 AN: 15104

Ashkenazi Jewish (ASJ) AF: 0.711 AC: 2448 AN: 3444

East Asian (EAS) AF: 0.737 AC: 3766 AN: 5112

South Asian (SAS) AF: 0.663 AC: 3162 AN: 4768

European-Finnish (FIN) AF: 0.760 AC: 7706 AN: 10144

Middle Eastern (MID) AF: 0.645 AC: 187 AN: 290

European-Non Finnish (NFE) AF: 0.722 AC: 48566 AN: 67302

Other (OTH) AF: 0.727 AC: 1510 AN: 2076

Alfa AF: 0.718 Hom.: 4049

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.13
DANN	Benign	0.73
PhyloP100		-0.079
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: rs1059804; hg19: chr22-38615536;