rs1060180

Positions:

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

Variant summary

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

The NM_004627.6(GET1):​c.*152G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 764,006 control chromosomes in the GnomAD database, including 178,322 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 0.65 (32628 hom., cov: 31)
  • Exomes 𝑓: 0.69 (145694 hom.)
• Consequence: GET1 NM_004627.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.904

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GET1	NM_004627.6	c.*152G>T		3_prime_UTR_variant	5/5	ENST00000649170.1	NP_004618.2
GET1-SH3BGR	NR_146618.2	n.510+3811G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GET1	ENST00000649170.1	c.*152G>T		3_prime_UTR_variant	5/5		NM_004627.6	ENSP00000496813	P1

Frequencies

GnomAD3 genomes AF: 0.650 AC: 98678 AN: 151814 Hom.: 32602 Cov.: 31

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.739

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.710

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.668

GnomAD4 exome AF: 0.686 AC: 420032 AN: 612074 Hom.: 145694 Cov.: 8 AF XY: 0.688 AC XY: 218829 AN XY: 318152

Gnomad4 AFR exome AF: 0.528

Gnomad4 AMR exome AF: 0.713

Gnomad4 ASJ exome AF: 0.659

Gnomad4 EAS exome AF: 0.802

Gnomad4 SAS exome AF: 0.707

Gnomad4 FIN exome AF: 0.776

Gnomad4 NFE exome AF: 0.675

Gnomad4 OTH exome AF: 0.669

GnomAD4 genome AF: 0.650 AC: 98751 AN: 151932 Hom.: 32628 Cov.: 31 AF XY: 0.659 AC XY: 48924 AN XY: 74282

Gnomad4 AFR AF: 0.524

Gnomad4 AMR AF: 0.692

Gnomad4 ASJ AF: 0.654

Gnomad4 EAS AF: 0.776

Gnomad4 SAS AF: 0.710

Gnomad4 FIN AF: 0.779

Gnomad4 NFE AF: 0.681

Gnomad4 OTH AF: 0.668

Alfa AF: 0.659 Hom.: 11110

Bravo AF: 0.640

Asia WGS AF: 0.746 AC: 2593 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.4
DANN	Benign	0.61
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

Publications

LitVar

Other links and lift over

dbSNP: rs1060180; hg19: chr21-40769017;