rs3786310

chr18-32392761-A-Gchr18-32392761-A-T

Variant summary

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

The NM_001242409.2(GAREM1):c.262+134T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 903,690 control chromosomes in the GnomAD database, including 6,154 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 0.13 (1575 hom., cov: 32)
  • Exomes 𝑓: 0.11 (4579 hom.)
• Consequence: GAREM1 NM_001242409.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.285

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAREM1	NM_001242409.2	c.262+134T>C		intron_variant		ENST00000269209.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAREM1	ENST00000269209.7	c.262+134T>C		intron_variant		1	NM_001242409.2	P4
GAREM1	ENST00000399218.8	c.262+134T>C		intron_variant		2		A1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20256 AN: 152108 Hom.: 1557 Cov.: 32

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0980

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0960

Gnomad OTH AF: 0.119

GnomAD4 exome AF: 0.106 AC: 79375 AN: 751464 Hom.: 4579 AF XY: 0.105 AC XY: 39516 AN XY: 378016

Gnomad4 AFR exome AF: 0.207

Gnomad4 AMR exome AF: 0.105

Gnomad4 ASJ exome AF: 0.0999

Gnomad4 EAS exome AF: 0.184

Gnomad4 SAS exome AF: 0.112

Gnomad4 FIN exome AF: 0.116

Gnomad4 NFE exome AF: 0.0957

Gnomad4 OTH exome AF: 0.113

GnomAD4 genome AF: 0.134 AC: 20339 AN: 152226 Hom.: 1575 Cov.: 32 AF XY: 0.134 AC XY: 10009 AN XY: 74442

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.0980

Gnomad4 EAS AF: 0.171

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.0960

Gnomad4 OTH AF: 0.125

Alfa AF: 0.0914 Hom.: 398

Bravo AF: 0.138

Asia WGS AF: 0.171 AC: 592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.0
Dann	Benign	0.48

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: rs3786310; hg19: chr18-29972724; COSMIC: COSV52508456;