18-32340467-C-T

Position:

• chr18-32340467-C-T

Variant summary

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

The NM_001242409.2(GAREM1):​c.263-30144G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 151,962 control chromosomes in the GnomAD database, including 928 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 0.11 (928 hom., cov: 32)
• Consequence: GAREM1 NM_001242409.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70

Genes affected

GAREM1 (HGNC:26136): (GRB2 associated regulator of MAPK1 subtype 1) This gene encodes an adaptor protein which functions in the epidermal growth factor (EGF) receptor-mediated signaling pathway. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAREM1	NM_001242409.2	c.263-30144G>A		intron_variant		ENST00000269209.7	NP_001229338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAREM1	ENST00000269209.7	c.263-30144G>A		intron_variant		1	NM_001242409.2	ENSP00000269209	P4
GAREM1	ENST00000399218.8	c.263-30144G>A		intron_variant		2		ENSP00000382165	A1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15919 AN: 151844 Hom.: 921 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0891

Gnomad ASJ AF: 0.0920

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0841

Gnomad OTH AF: 0.0921

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

GnomAD4 genome AF: 0.105 AC: 15958 AN: 151962 Hom.: 928 Cov.: 32 AF XY: 0.107 AC XY: 7925 AN XY: 74246

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.0889

Gnomad4 ASJ AF: 0.0920

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.0841

Gnomad4 OTH AF: 0.0983

Alfa AF: 0.0904 Hom.: 808

Bravo AF: 0.106

Asia WGS AF: 0.153 AC: 529 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.084
DANN	Benign	0.71

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: rs10502587; hg19: chr18-29920430;