rs2076189

Variant names:

• chr6-11778855-C-A
• rs2076189
• ENST00000379415.6:c.-96G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-11778855-C-A
• chr6-11778855-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000506810.1(ADTRP):​c.-96G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000824 in 1,213,350 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 8.2e-7 (0 hom.)
• Consequence: ADTRP ENST00000506810.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.628
• Publications: 0 publications found

Genes affected

ADTRP (HGNC:21214): (androgen dependent TFPI regulating protein) Enables hydrolase activity. Involved in several processes, including cell migration involved in sprouting angiogenesis; negative regulation of secretion by cell; and positive regulation of macromolecule metabolic process. Located in caveola and cell surface. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000506810.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADTRP	NM_032744.4	MANE Select	c.-96G>T		upstream_gene	N/A	NP_116133.1	Q96IZ2-1
	ADTRP	NM_001143948.2		c.-96G>T		upstream_gene	N/A	NP_001137420.1	Q96IZ2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADTRP	ENST00000379415.6	TSL:5	c.-96G>T		5_prime_UTR	Exon 3 of 6	ENSP00000368726.2	D6R9A9
	ADTRP	ENST00000506810.1	TSL:3	c.-96G>T		5_prime_UTR	Exon 2 of 5	ENSP00000422927.1	D6R9A9
	ADTRP	ENST00000414691.8	TSL:1 MANE Select	c.-96G>T		upstream_gene	N/A	ENSP00000404416.2	Q96IZ2-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.24e-7 AC: 1 AN: 1213350 Hom.: 0 Cov.: 15 AF XY: 0.00000166 AC XY: 1 AN XY: 600932

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 27756

American (AMR) AF: 0.00 AC: 0 AN: 31832

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20152

East Asian (EAS) AF: 0.00 AC: 0 AN: 36944

South Asian (SAS) AF: 0.00 AC: 0 AN: 64588

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49144

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3846

European-Non Finnish (NFE) AF: 0.00000108 AC: 1 AN: 928164

Other (OTH) AF: 0.00 AC: 0 AN: 50924

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.038
DANN	Benign	0.64
PhyloP100		-0.63
PromoterAI		0.033	Neutral

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2076189;

hg19: chr6-11779088;