20-3560986-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATRN	NM_139321.3	c.1447+81A>G		intron_variant		ENST00000262919.10
ATRN	NM_001207047.3	c.1099+81A>G		intron_variant
ATRN	NM_001323332.2	c.1447+81A>G		intron_variant
ATRN	NM_139322.4	c.1447+81A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATRN	ENST00000262919.10	c.1447+81A>G		intron_variant		5	NM_139321.3	P2
ATRN	ENST00000446916.2	c.1447+81A>G		intron_variant		1		A2

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

Gnomad4 AFR exome AF: 0.940

Gnomad4 AMR exome AF: 0.895

Gnomad4 ASJ exome AF: 0.775

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.940

Gnomad4 FIN exome AF: 0.849

Gnomad4 NFE exome AF: 0.787

Gnomad4 OTH exome AF: 0.831

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

Gnomad4 AFR AF: 0.934

Gnomad4 AMR AF: 0.858

Gnomad4 ASJ AF: 0.773

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.946

Gnomad4 FIN AF: 0.858

Gnomad4 NFE AF: 0.799

Gnomad4 OTH AF: 0.836

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.26
Dann	Benign	0.35

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: rs235577; hg19: chr20-3541633;