chr18-32455940-T-G

Variant names:

• chr18-32455940-T-G
• rs10502602
• NM_001242409.2:c.121+14368A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001242409.2(GAREM1):​c.121+14368A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 151,994 control chromosomes in the GnomAD database, including 2,823 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 0.19 (2823 hom., cov: 32)
• Consequence: GAREM1 NM_001242409.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.621
• 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=-0.69).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.234 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.121+14368A>C		intron	N/A	NP_001229338.1
	GAREM1	NM_022751.3		c.121+14368A>C		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.121+14368A>C		intron	N/A	ENSP00000269209.6
	GAREM1	ENST00000399218.8	TSL:2	c.121+14368A>C		intron	N/A	ENSP00000382165.3

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28215 AN: 151876 Hom.: 2819 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.0962

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.186 AC: 28240 AN: 151994 Hom.: 2823 Cov.: 32 AF XY: 0.188 AC XY: 13992 AN XY: 74290

African (AFR) AF: 0.230 AC: 9542 AN: 41470

American (AMR) AF: 0.240 AC: 3667 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 509 AN: 3472

East Asian (EAS) AF: 0.167 AC: 862 AN: 5172

South Asian (SAS) AF: 0.0963 AC: 463 AN: 4810

European-Finnish (FIN) AF: 0.191 AC: 2017 AN: 10576

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10567 AN: 67924

Other (OTH) AF: 0.180 AC: 380 AN: 2114

Alfa AF: 0.162 Hom.: 4107

Bravo AF: 0.194

Asia WGS AF: 0.112 AC: 389 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.91
DANN	Benign	0.76
PhyloP100		-0.62
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: rs10502602; hg19: chr18-30035903;