rs17782078

Variant names:

• chr20-3560735-T-C
• rs17782078
• NM_139321.3:c.1277T>C

Your query was ambiguous. Multiple possible variants found:

• chr20-3560735-T-C
• chr20-3560735-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_139321.3(ATRN):​c.1277T>C​(p.Ile426Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0476 in 1,613,938 control chromosomes in the GnomAD database, including 2,114 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (146 hom., cov: 32)
  • Exomes 𝑓: 0.049 (1968 hom.)
• Consequence: ATRN NM_139321.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 5.99
• Publications: 18 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003145665).
• BP6: Variant 20-3560735-T-C is Benign according to our data. Variant chr20-3560735-T-C is described in ClinVar as Benign. ClinVar VariationId is 1167765.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0545 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATRN	NM_139321.3	MANE Select	c.1277T>C	p.Ile426Thr	missense	Exon 8 of 29	NP_647537.1
	ATRN	NM_001323332.2		c.1277T>C	p.Ile426Thr	missense	Exon 8 of 26	NP_001310261.1
	ATRN	NM_139322.4		c.1277T>C	p.Ile426Thr	missense	Exon 8 of 25	NP_647538.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATRN	ENST00000262919.10	TSL:5 MANE Select	c.1277T>C	p.Ile426Thr	missense	Exon 8 of 29	ENSP00000262919.5
	ATRN	ENST00000446916.2	TSL:1	c.1277T>C	p.Ile426Thr	missense	Exon 8 of 25	ENSP00000416587.2

Frequencies

GnomAD3 genomes AF: 0.0380 AC: 5783 AN: 152134 Hom.: 146 Cov.: 32

Gnomad AFR AF: 0.00936

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.0406

Gnomad ASJ AF: 0.0274

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0106

Gnomad FIN AF: 0.0609

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0560

Gnomad OTH AF: 0.0406

GnomAD2 exomes AF: 0.0393 AC: 9871 AN: 251290 AF XY: 0.0395

Gnomad AFR exome AF: 0.00837

Gnomad AMR exome AF: 0.0288

Gnomad ASJ exome AF: 0.0331

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0684

Gnomad NFE exome AF: 0.0559

Gnomad OTH exome AF: 0.0440

GnomAD4 exome AF: 0.0487 AC: 71114 AN: 1461686 Hom.: 1968 Cov.: 32 AF XY: 0.0478 AC XY: 34757 AN XY: 727156

African (AFR) AF: 0.00824 AC: 276 AN: 33480

American (AMR) AF: 0.0297 AC: 1328 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0337 AC: 880 AN: 26132

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39698

South Asian (SAS) AF: 0.00976 AC: 842 AN: 86258

European-Finnish (FIN) AF: 0.0688 AC: 3673 AN: 53418

Middle Eastern (MID) AF: 0.0201 AC: 116 AN: 5768

European-Non Finnish (NFE) AF: 0.0553 AC: 61450 AN: 1111824

Other (OTH) AF: 0.0422 AC: 2546 AN: 60386

GnomAD4 genome AF: 0.0380 AC: 5781 AN: 152252 Hom.: 146 Cov.: 32 AF XY: 0.0376 AC XY: 2799 AN XY: 74444

African (AFR) AF: 0.00934 AC: 388 AN: 41556

American (AMR) AF: 0.0405 AC: 619 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0274 AC: 95 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.0106 AC: 51 AN: 4824

European-Finnish (FIN) AF: 0.0609 AC: 646 AN: 10600

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0560 AC: 3810 AN: 67998

Other (OTH) AF: 0.0402 AC: 85 AN: 2116

Alfa AF: 0.0486 Hom.: 584

Bravo AF: 0.0354

TwinsUK AF: 0.0545 AC: 202

ALSPAC AF: 0.0610 AC: 235

ESP6500AA AF: 0.0102 AC: 45

ESP6500EA AF: 0.0563 AC: 484

ExAC AF: 0.0387 AC: 4694

Asia WGS AF: 0.00722 AC: 25 AN: 3478

EpiCase AF: 0.0556

EpiControl AF: 0.0586

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	ATRN-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.072
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.93	D
MetaRNN	Benign	0.0031	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.89	L
PhyloP100		6.0
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.14
Sift	Benign	0.16	T
Sift4G	Benign	0.32	T
Polyphen		0.080	B
Vest4		0.18
MPC		0.20
ClinPred		0.014	T
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.29
gMVP		0.83
Mutation Taster		=93/7	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: rs17782078; hg19: chr20-3541382; COSMIC: COSV107302531;