18-32455940-T-G

Position:

• chr18-32455940-T-G

Variant summary

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

The ENST00000269209.7(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 ENST00000269209.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.621

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=-0.69).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAREM1	NM_001242409.2	c.121+14368A>C		intron_variant		ENST00000269209.7	NP_001229338.1
GAREM1	NM_022751.3	c.121+14368A>C		intron_variant			NP_073588.1
GAREM1	XM_017025919.2	c.121+14368A>C		intron_variant			XP_016881408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAREM1	ENST00000269209.7	c.121+14368A>C		intron_variant		1	NM_001242409.2	ENSP00000269209	P4
GAREM1	ENST00000399218.8	c.121+14368A>C		intron_variant		2		ENSP00000382165	A1

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

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.0963

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.180

Alfa AF: 0.159 Hom.: 2883

Bravo AF: 0.194

Asia WGS AF: 0.112 AC: 389 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.91
DANN	Benign	0.76

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: rs10502602; hg19: chr18-30035903;