rs16963279

Variant names:

• chr18-32370661-C-T
• rs16963279
• NM_001242409.2:c.262+22234G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242409.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAREM1	NM_001242409.2	MANE Select	c.262+22234G>A		intron	N/A	NP_001229338.1
	GAREM1	NM_022751.3		c.262+22234G>A		intron	N/A	NP_073588.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAREM1	ENST00000269209.7	TSL:1 MANE Select	c.262+22234G>A		intron	N/A	ENSP00000269209.6
	GAREM1	ENST00000399218.8	TSL:2	c.262+22234G>A		intron	N/A	ENSP00000382165.3

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

African (AFR) AF: 0.191 AC: 7928 AN: 41460

American (AMR) AF: 0.0538 AC: 822 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0239 AC: 83 AN: 3472

East Asian (EAS) AF: 0.00830 AC: 43 AN: 5182

South Asian (SAS) AF: 0.0459 AC: 221 AN: 4810

European-Finnish (FIN) AF: 0.0835 AC: 882 AN: 10560

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0438 AC: 2979 AN: 68026

Other (OTH) AF: 0.0682 AC: 144 AN: 2110

Alfa AF: 0.0782 Hom.: 131

Bravo AF: 0.0901

Asia WGS AF: 0.0360 AC: 124 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.67
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16963279; hg19: chr18-29950624;