18-32177170-T-G

Variant names:

• chr18-32177170-T-G
• rs10502583
• ENST00000583696.1:c.64-40710A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000583696.1(GAREM1):​c.64-40710A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 151,520 control chromosomes in the GnomAD database, including 1,407 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 0.12 (1407 hom., cov: 33)
• Consequence: GAREM1 ENST00000583696.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.166
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAREM1	ENST00000583696.1	c.64-40710A>C		intron_variant	Intron 1 of 2	3		ENSP00000464185.1

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17931 AN: 151400 Hom.: 1406 Cov.: 33

Gnomad AFR AF: 0.0352

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.00557

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.118 AC: 17934 AN: 151520 Hom.: 1407 Cov.: 33 AF XY: 0.117 AC XY: 8646 AN XY: 74002

African (AFR) AF: 0.0351 AC: 1456 AN: 41486

American (AMR) AF: 0.102 AC: 1545 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 607 AN: 3460

East Asian (EAS) AF: 0.00559 AC: 29 AN: 5190

South Asian (SAS) AF: 0.197 AC: 939 AN: 4760

European-Finnish (FIN) AF: 0.139 AC: 1464 AN: 10526

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11515 AN: 67594

Other (OTH) AF: 0.115 AC: 240 AN: 2090

Alfa AF: 0.157 Hom.: 1808

Bravo AF: 0.110

Asia WGS AF: 0.0510 AC: 171 AN: 3326

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.4
DANN	Benign	0.78
PhyloP100		-0.17

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10502583; hg19: chr18-29757133;