20-3560986-A-G

Variant names:

• chr20-3560986-A-G
• rs235577
• NM_139321.3:c.1447+81A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139321.3(ATRN):​c.1447+81A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.817 in 1,514,376 control chromosomes in the GnomAD database, including 508,435 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 0.86 (56455 hom., cov: 31)
  • Exomes 𝑓: 0.81 (451980 hom.)
• Consequence: ATRN NM_139321.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.926
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 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.1447+81A>G		intron	N/A	NP_647537.1
	ATRN	NM_001323332.2		c.1447+81A>G		intron	N/A	NP_001310261.1
	ATRN	NM_139322.4		c.1447+81A>G		intron	N/A	NP_647538.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATRN	ENST00000262919.10	TSL:5 MANE Select	c.1447+81A>G		intron	N/A	ENSP00000262919.5
	ATRN	ENST00000446916.2	TSL:1	c.1447+81A>G		intron	N/A	ENSP00000416587.2

Frequencies

GnomAD3 genomes AF: 0.858 AC: 130503 AN: 152120 Hom.: 56396 Cov.: 31

Gnomad AFR AF: 0.934

Gnomad AMI AF: 0.905

Gnomad AMR AF: 0.857

Gnomad ASJ AF: 0.773

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.946

Gnomad FIN AF: 0.858

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.799

Gnomad OTH AF: 0.834

GnomAD4 exome AF: 0.813 AC: 1107040 AN: 1362138 Hom.: 451980 AF XY: 0.817 AC XY: 550961 AN XY: 674652

African (AFR) AF: 0.940 AC: 29038 AN: 30900

American (AMR) AF: 0.895 AC: 35368 AN: 39532

Ashkenazi Jewish (ASJ) AF: 0.775 AC: 17604 AN: 22712

East Asian (EAS) AF: 1.00 AC: 38864 AN: 38882

South Asian (SAS) AF: 0.940 AC: 72600 AN: 77232

European-Finnish (FIN) AF: 0.849 AC: 43063 AN: 50740

Middle Eastern (MID) AF: 0.861 AC: 4691 AN: 5450

European-Non Finnish (NFE) AF: 0.787 AC: 818897 AN: 1040258

Other (OTH) AF: 0.831 AC: 46915 AN: 56432

GnomAD4 genome AF: 0.858 AC: 130622 AN: 152238 Hom.: 56455 Cov.: 31 AF XY: 0.862 AC XY: 64133 AN XY: 74426

African (AFR) AF: 0.934 AC: 38788 AN: 41542

American (AMR) AF: 0.858 AC: 13116 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.773 AC: 2685 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5173 AN: 5182

South Asian (SAS) AF: 0.946 AC: 4567 AN: 4828

European-Finnish (FIN) AF: 0.858 AC: 9084 AN: 10586

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.799 AC: 54361 AN: 68016

Other (OTH) AF: 0.836 AC: 1766 AN: 2112

Alfa AF: 0.832 Hom.: 7608

Bravo AF: 0.859

Asia WGS AF: 0.977 AC: 3398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.26
DANN	Benign	0.35
PhyloP100		-0.93
Mutation Taster		=100/0	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: rs235577; hg19: chr20-3541633;