rs169790

Positions:

• chr6-11714058-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_032744.4(ADTRP):​c.*420C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00675 in 163,480 control chromosomes in the GnomAD database, including 34 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 0.0071 (34 hom., cov: 31)
  • Exomes 𝑓: 0.0019 (0 hom.)
• Consequence: ADTRP NM_032744.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00711 (1081/152122) while in subpopulation AMR AF= 0.0469 (716/15278). AF 95% confidence interval is 0.044. There are 34 homozygotes in gnomad4. There are 610 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 34 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADTRP	NM_032744.4	c.*420C>T		3_prime_UTR_variant	6/6	ENST00000414691.8	NP_116133.1
ADTRP	NM_001143948.2	c.*420C>T		3_prime_UTR_variant	7/7		NP_001137420.1
ADTRP	XM_011514956.2	c.*451C>T		3_prime_UTR_variant	7/7		XP_011513258.1
ADTRP	XM_047419420.1	c.*451C>T		3_prime_UTR_variant	7/7		XP_047275376.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADTRP	ENST00000414691.8	c.*420C>T		3_prime_UTR_variant	6/6	1	NM_032744.4	ENSP00000404416	P1
ADTRP	ENST00000513651.5	n.838C>T		non_coding_transcript_exon_variant	3/3	1
ADTRP	ENST00000514824.5	n.1540C>T		non_coding_transcript_exon_variant	5/5	2
ADTRP	ENST00000505099.5	c.*144+276C>T		intron_variant, NMD_transcript_variant		3		ENSP00000424680

Frequencies

GnomAD3 genomes AF: 0.00708 AC: 1077 AN: 152014 Hom.: 34 Cov.: 31

Gnomad AFR AF: 0.000967

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0467

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0439

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.00170

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000676

Gnomad OTH AF: 0.00814

GnomAD4 exome AF: 0.00194 AC: 22 AN: 11358 Hom.: 0 Cov.: 0 AF XY: 0.00262 AC XY: 16 AN XY: 6106

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0309

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0144

Gnomad4 SAS exome AF: 0.00166

Gnomad4 FIN exome AF: 0.00182

Gnomad4 NFE exome AF: 0.000990

Gnomad4 OTH exome AF: 0.00262

GnomAD4 genome AF: 0.00711 AC: 1081 AN: 152122 Hom.: 34 Cov.: 31 AF XY: 0.00820 AC XY: 610 AN XY: 74368

Gnomad4 AFR AF: 0.000964

Gnomad4 AMR AF: 0.0469

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0438

Gnomad4 SAS AF: 0.00332

Gnomad4 FIN AF: 0.00170

Gnomad4 NFE AF: 0.000676

Gnomad4 OTH AF: 0.00853

Alfa AF: 0.00695 Hom.: 11

Bravo AF: 0.0111

Asia WGS AF: 0.0150 AC: 52 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.52
DANN	Benign	0.41

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: rs169790; hg19: chr6-11714291;