18-32392811-T-C

Position:

• chr18-32392811-T-C

Variant summary

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

The NM_001242409.2(GAREM1):​c.262+84A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 1,431,734 control chromosomes in the GnomAD database, including 182,449 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 0.39 (14416 hom., cov: 32)
  • Exomes 𝑓: 0.50 (168033 hom.)
• Consequence: GAREM1 NM_001242409.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAREM1	NM_001242409.2	c.262+84A>G		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+84A>G		intron_variant		1	NM_001242409.2	ENSP00000269209.6
GAREM1	ENST00000399218.8	c.262+84A>G		intron_variant		2		ENSP00000382165.3

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59367 AN: 152010 Hom.: 14418 Cov.: 32

Gnomad AFR AF: 0.0969

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.426

GnomAD4 exome AF: 0.505 AC: 646059 AN: 1279606 Hom.: 168033 AF XY: 0.505 AC XY: 320881 AN XY: 634918

Gnomad4 AFR exome AF: 0.0827

Gnomad4 AMR exome AF: 0.398

Gnomad4 ASJ exome AF: 0.517

Gnomad4 EAS exome AF: 0.313

Gnomad4 SAS exome AF: 0.454

Gnomad4 FIN exome AF: 0.535

Gnomad4 NFE exome AF: 0.533

Gnomad4 OTH exome AF: 0.483

GnomAD4 genome AF: 0.390 AC: 59356 AN: 152128 Hom.: 14416 Cov.: 32 AF XY: 0.392 AC XY: 29126 AN XY: 74366

Gnomad4 AFR AF: 0.0966

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.516

Gnomad4 EAS AF: 0.297

Gnomad4 SAS AF: 0.446

Gnomad4 FIN AF: 0.532

Gnomad4 NFE AF: 0.533

Gnomad4 OTH AF: 0.421

Alfa AF: 0.492 Hom.: 11485

Bravo AF: 0.365

Asia WGS AF: 0.368 AC: 1285 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.2
DANN	Benign	0.64

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: rs3786309; hg19: chr18-29972774;