rs10502593

Positions:

• chr18-32386565-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+6330G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0348 in 152,248 control chromosomes in the GnomAD database, including 143 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 0.035 (143 hom., cov: 32)
• Consequence: GAREM1 NM_001242409.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.419

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=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAREM1	NM_001242409.2	c.262+6330G>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.262+6330G>A		intron_variant		1	NM_001242409.2	ENSP00000269209.6
GAREM1	ENST00000399218.8	c.262+6330G>A		intron_variant		2		ENSP00000382165.3

Frequencies

GnomAD3 genomes AF: 0.0348 AC: 5295 AN: 152130 Hom.: 143 Cov.: 32

Gnomad AFR AF: 0.0371

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.0385

Gnomad ASJ AF: 0.0181

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.0354

Gnomad FIN AF: 0.0770

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0210

Gnomad OTH AF: 0.0325

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

GnomAD4 genome AF: 0.0348 AC: 5304 AN: 152248 Hom.: 143 Cov.: 32 AF XY: 0.0376 AC XY: 2801 AN XY: 74436

Gnomad4 AFR AF: 0.0371

Gnomad4 AMR AF: 0.0385

Gnomad4 ASJ AF: 0.0181

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.0361

Gnomad4 FIN AF: 0.0770

Gnomad4 NFE AF: 0.0210

Gnomad4 OTH AF: 0.0341

Alfa AF: 0.0266 Hom.: 15

Bravo AF: 0.0342

Asia WGS AF: 0.0710 AC: 247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.1
DANN	Benign	0.75

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: rs10502593; hg19: chr18-29966528;