rs1060180

Variant names:

• chr21-39397091-G-C
• rs1060180
• ENST00000466787.1:n.*978G>C

Your query was ambiguous. Multiple possible variants found:

• chr21-39397091-G-C
• chr21-39397091-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000466787.1(GET1):​n.*978G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000163 in 613,052 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: GET1 ENST00000466787.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.904
• Publications: 17 publications found

Genes affected

GET1 (HGNC:12790): (guided entry of tail-anchored proteins factor 1) This gene is located in the candidate region for congenital heart disease (CHD) in Down syndrome (DS). It encodes a basic protein that functions as a receptor that promotes insertion of tail-anchored proteins in the endoplasmic reticulum membrane. This gene is located at a maternally-methylated differentially methylated region (DMR); however, its transcription may be biallelic, not imprinted. Alternative splicing results in different transcript variants. A pseudogene has been defined on chromosome 4. [provided by RefSeq, Apr 2017]

GET1-SH3BGR (HGNC:54635): (GET1-SH3BGR readthrough) This locus represents naturally occurring readthrough transcription between the neighboring WRB (tryptophan rich basic protein) and SH3BGR (SH3 domain binding glutamate-rich protein) genes on chromosome 21. Readthrough transcripts may encode fusion proteins that shares sequence identity with each individual gene product. [provided by RefSeq, Apr 2017]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GET1	NM_004627.6	c.*152G>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000649170.1	NP_004618.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GET1	ENST00000649170.1	c.*152G>C		3_prime_UTR_variant	Exon 5 of 5		NM_004627.6	ENSP00000496813.1
GET1-SH3BGR	ENST00000647779.1	c.336+5255G>C		intron_variant	Intron 3 of 8			ENSP00000497977.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000163 AC: 1 AN: 613052 Hom.: 0 Cov.: 8 AF XY: 0.00000314 AC XY: 1 AN XY: 318618

African (AFR) AF: 0.00 AC: 0 AN: 15172

American (AMR) AF: 0.00 AC: 0 AN: 19752

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14980

East Asian (EAS) AF: 0.0000312 AC: 1 AN: 32064

South Asian (SAS) AF: 0.00 AC: 0 AN: 48798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33020

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2924

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 415168

Other (OTH) AF: 0.00 AC: 0 AN: 31174

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.6
DANN	Benign	0.57
PhyloP100		0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1060180; hg19: chr21-40769017;