20-3471261-C-T

Variant names:

• chr20-3471261-C-T
• rs6051882
• NM_139321.3:c.154C>T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_139321.3(ATRN):​c.154C>T​(p.Leu52Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0128 in 1,448,050 control chromosomes in the GnomAD database, including 1,281 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.055 (726 hom., cov: 33)
  • Exomes 𝑓: 0.0078 (555 hom.)
• Consequence: ATRN NM_139321.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.316

Genes affected

ATRN (HGNC:885): (attractin) This gene encodes both membrane-bound and secreted protein isoforms. A membrane-bound isoform exhibits sequence similarity with the mouse mahogany protein, a receptor involved in controlling obesity. A secreted isoform is involved in the initial immune cell clustering during inflammatory responses that may regulate the chemotactic activity of chemokines. [provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 20-3471261-C-T is Benign according to our data. Variant chr20-3471261-C-T is described in ClinVar as [Benign]. Clinvar id is 1167763.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.316 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATRN	NM_139321.3	c.154C>T	p.Leu52Leu	synonymous_variant	Exon 1 of 29	ENST00000262919.10	NP_647537.1
ATRN	NM_001323332.2	c.154C>T	p.Leu52Leu	synonymous_variant	Exon 1 of 26		NP_001310261.1
ATRN	NM_139322.4	c.154C>T	p.Leu52Leu	synonymous_variant	Exon 1 of 25		NP_647538.1
ATRN	NM_001207047.3	c.62+127C>T		intron_variant	Intron 1 of 24		NP_001193976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATRN	ENST00000262919.10	c.154C>T	p.Leu52Leu	synonymous_variant	Exon 1 of 29	5	NM_139321.3	ENSP00000262919.5
ATRN	ENST00000446916.2	c.154C>T	p.Leu52Leu	synonymous_variant	Exon 1 of 25	1		ENSP00000416587.2

Frequencies

GnomAD3 genomes AF: 0.0550 AC: 8370 AN: 152070 Hom.: 721 Cov.: 33

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0219

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0337

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0541

Gnomad NFE AF: 0.00240

Gnomad OTH AF: 0.0455

GnomAD3 exomes AF: 0.0139 AC: 687 AN: 49504 Hom.: 22 AF XY: 0.0143 AC XY: 413 AN XY: 28796

Gnomad AFR exome AF: 0.190

Gnomad AMR exome AF: 0.0113

Gnomad ASJ exome AF: 0.000277

Gnomad EAS exome AF: 0.000485

Gnomad SAS exome AF: 0.0367

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00288

Gnomad OTH exome AF: 0.0135

GnomAD4 exome AF: 0.00777 AC: 10066 AN: 1295872 Hom.: 555 Cov.: 32 AF XY: 0.00802 AC XY: 5107 AN XY: 637104

Gnomad4 AFR exome AF: 0.190

Gnomad4 AMR exome AF: 0.0133

Gnomad4 ASJ exome AF: 0.000192

Gnomad4 EAS exome AF: 0.0000349

Gnomad4 SAS exome AF: 0.0350

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00148

Gnomad4 OTH exome AF: 0.0165

GnomAD4 genome AF: 0.0552 AC: 8404 AN: 152178 Hom.: 726 Cov.: 33 AF XY: 0.0538 AC XY: 4007 AN XY: 74416

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.0219

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0337

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00240

Gnomad4 OTH AF: 0.0450

Alfa AF: 0.00810 Hom.: 12

Bravo AF: 0.0623

Asia WGS AF: 0.0260 AC: 88 AN: 3460

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

ATRN-related disorder Benign:1

Jul 30, 2024

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	8.7
DANN	Benign	0.89

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: rs6051882; hg19: chr20-3451908;