rs16963279

Positions:

• chr18-32370661-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+22234G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0872 in 152,116 control chromosomes in the GnomAD database, including 907 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 0.087 (907 hom., cov: 32)
• Consequence: GAREM1 NM_001242409.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.185

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAREM1	NM_001242409.2	c.262+22234G>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+22234G>A		intron_variant		1	NM_001242409.2	ENSP00000269209	P4
GAREM1	ENST00000399218.8	c.262+22234G>A		intron_variant		2		ENSP00000382165	A1

Frequencies

GnomAD3 genomes AF: 0.0870 AC: 13231 AN: 151998 Hom.: 902 Cov.: 32

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.0539

Gnomad ASJ AF: 0.0239

Gnomad EAS AF: 0.00847

Gnomad SAS AF: 0.0457

Gnomad FIN AF: 0.0835

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0438

Gnomad OTH AF: 0.0685

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

GnomAD4 genome AF: 0.0872 AC: 13261 AN: 152116 Hom.: 907 Cov.: 32 AF XY: 0.0878 AC XY: 6534 AN XY: 74388

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.0538

Gnomad4 ASJ AF: 0.0239

Gnomad4 EAS AF: 0.00830

Gnomad4 SAS AF: 0.0459

Gnomad4 FIN AF: 0.0835

Gnomad4 NFE AF: 0.0438

Gnomad4 OTH AF: 0.0682

Alfa AF: 0.0748 Hom.: 118

Bravo AF: 0.0901

Asia WGS AF: 0.0360 AC: 124 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.67

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: rs16963279; hg19: chr18-29950624;