18-32390023-C-T

Position:

• chr18-32390023-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.262+2872G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 151,822 control chromosomes in the GnomAD database, including 1,575 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: 31)
• Consequence: GAREM1 NM_001242409.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.190

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=-1.0).
• 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+2872G>A		intron_variant		ENST00000269209.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAREM1	ENST00000269209.7	c.262+2872G>A		intron_variant		1	NM_001242409.2	P4
GAREM1	ENST00000399218.8	c.262+2872G>A		intron_variant		2		A1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20220 AN: 151704 Hom.: 1557 Cov.: 31

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.0527

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0981

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0573

Gnomad NFE AF: 0.0961

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.134 AC: 20303 AN: 151822 Hom.: 1575 Cov.: 31 AF XY: 0.134 AC XY: 9970 AN XY: 74182

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.0981

Gnomad4 EAS AF: 0.171

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.0961

Gnomad4 OTH AF: 0.125

Alfa AF: 0.103 Hom.: 1424

Bravo AF: 0.138

Asia WGS AF: 0.171 AC: 594 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.8
DANN	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs13381088; hg19: chr18-29969986;