rs235590

Positions:

• chr20-3553693-G-A
• chr20-3553693-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139321.3(ATRN):​c.1112+4355G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.84 in 152,194 control chromosomes in the GnomAD database, including 53,969 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 0.84 (53969 hom., cov: 31)
• Consequence: ATRN NM_139321.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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=-0.87).
• 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	Protein	UniProt
ATRN	NM_139321.3	c.1112+4355G>A		intron_variant		ENST00000262919.10	NP_647537.1
ATRN	NM_001207047.3	c.764+4355G>A		intron_variant			NP_001193976.1
ATRN	NM_001323332.2	c.1112+4355G>A		intron_variant			NP_001310261.1
ATRN	NM_139322.4	c.1112+4355G>A		intron_variant			NP_647538.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATRN	ENST00000262919.10	c.1112+4355G>A		intron_variant		5	NM_139321.3	ENSP00000262919	P2
ATRN	ENST00000446916.2	c.1112+4355G>A		intron_variant		1		ENSP00000416587	A2

Frequencies

GnomAD3 genomes AF: 0.840 AC: 127716 AN: 152076 Hom.: 53907 Cov.: 31

Gnomad AFR AF: 0.871

Gnomad AMI AF: 0.905

Gnomad AMR AF: 0.850

Gnomad ASJ AF: 0.773

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.950

Gnomad FIN AF: 0.858

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.799

Gnomad OTH AF: 0.823

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.840 AC: 127835 AN: 152194 Hom.: 53969 Cov.: 31 AF XY: 0.845 AC XY: 62843 AN XY: 74394

Gnomad4 AFR AF: 0.871

Gnomad4 AMR AF: 0.851

Gnomad4 ASJ AF: 0.773

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.950

Gnomad4 FIN AF: 0.858

Gnomad4 NFE AF: 0.799

Gnomad4 OTH AF: 0.825

Alfa AF: 0.828 Hom.: 8831

Bravo AF: 0.839

Asia WGS AF: 0.979 AC: 3403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.32
DANN	Benign	0.38

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: rs235590; hg19: chr20-3534340;