NM_139321.3:c.154C>T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139321.3. 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
	ATRN	NM_139321.3	MANE Select	c.154C>T	p.Leu52Leu	synonymous	Exon 1 of 29	NP_647537.1	O75882-1
	ATRN	NM_001323332.2		c.154C>T	p.Leu52Leu	synonymous	Exon 1 of 26	NP_001310261.1
	ATRN	NM_139322.4		c.154C>T	p.Leu52Leu	synonymous	Exon 1 of 25	NP_647538.1	O75882-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATRN	ENST00000262919.10	TSL:5 MANE Select	c.154C>T	p.Leu52Leu	synonymous	Exon 1 of 29	ENSP00000262919.5	O75882-1
	ATRN	ENST00000446916.2	TSL:1	c.154C>T	p.Leu52Leu	synonymous	Exon 1 of 25	ENSP00000416587.2	O75882-2
	ATRN	ENST00000928835.1		c.154C>T	p.Leu52Leu	synonymous	Exon 1 of 28	ENSP00000598894.1

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

GnomAD2 exomes AF: 0.0139 AC: 687 AN: 49504 AF XY: 0.0143

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 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

African (AFR) AF: 0.190 AC: 4891 AN: 25808

American (AMR) AF: 0.0133 AC: 280 AN: 21094

Ashkenazi Jewish (ASJ) AF: 0.000192 AC: 4 AN: 20822

East Asian (EAS) AF: 0.0000349 AC: 1 AN: 28684

South Asian (SAS) AF: 0.0350 AC: 2340 AN: 66888

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32196

Middle Eastern (MID) AF: 0.0317 AC: 123 AN: 3884

European-Non Finnish (NFE) AF: 0.00148 AC: 1540 AN: 1042580

Other (OTH) AF: 0.0165 AC: 887 AN: 53916

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

African (AFR) AF: 0.184 AC: 7632 AN: 41502

American (AMR) AF: 0.0219 AC: 335 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.0337 AC: 163 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.0514 AC: 15 AN: 292

European-Non Finnish (NFE) AF: 0.00240 AC: 163 AN: 67982

Other (OTH) AF: 0.0450 AC: 95 AN: 2112

Alfa AF: 0.00810 Hom.: 12

Bravo AF: 0.0623

Asia WGS AF: 0.0260 AC: 88 AN: 3460

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	ATRN-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	8.7
DANN	Benign	0.89
PhyloP100		0.32
PromoterAI		0.014	Neutral
Mutation Taster		=99/1	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: rs6051882; hg19: chr20-3451908;