rs902951

chr18-32359314-T-A

Variant summary

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

The NM_001242409.2(GAREM1):c.262+33581A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,130 control chromosomes in the GnomAD database, including 1,425 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 0.10 (1425 hom., cov: 32)
• Consequence: GAREM1 NM_001242409.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.624

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAREM1	NM_001242409.2	c.262+33581A>T		intron_variant		ENST00000269209.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAREM1	ENST00000269209.7	c.262+33581A>T		intron_variant		1	NM_001242409.2	P4
GAREM1	ENST00000399218.8	c.262+33581A>T		intron_variant		2		A1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15563 AN: 152012 Hom.: 1416 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.0583

Gnomad ASJ AF: 0.0239

Gnomad EAS AF: 0.00906

Gnomad SAS AF: 0.0624

Gnomad FIN AF: 0.0838

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0438

Gnomad OTH AF: 0.0832

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

GnomAD4 genome AF: 0.103 AC: 15619 AN: 152130 Hom.: 1425 Cov.: 32 AF XY: 0.103 AC XY: 7665 AN XY: 74388

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.0581

Gnomad4 ASJ AF: 0.0239

Gnomad4 EAS AF: 0.00889

Gnomad4 SAS AF: 0.0628

Gnomad4 FIN AF: 0.0838

Gnomad4 NFE AF: 0.0438

Gnomad4 OTH AF: 0.0828

Alfa AF: 0.0853 Hom.: 130

Bravo AF: 0.107

Asia WGS AF: 0.0460 AC: 160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.14
Dann	Benign	0.58

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: rs902951; hg19: chr18-29939277;