18-32390023-C-T

Variant names:

• chr18-32390023-C-T
• rs13381088
• NM_001242409.2:c.262+2872G>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+2872G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 151,822 control chromosomes in the GnomAD database, including 1,575 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 0.13 (1575 hom., cov: 31)
• Consequence: GAREM1 NM_001242409.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.190
• Publications: 1 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.208 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAREM1	NM_001242409.2	MANE Select	c.262+2872G>A		intron	N/A	NP_001229338.1	Q9H706-1
	GAREM1	NM_022751.3		c.262+2872G>A		intron	N/A	NP_073588.1	Q9H706-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAREM1	ENST00000269209.7	TSL:1 MANE Select	c.262+2872G>A		intron	N/A	ENSP00000269209.6	Q9H706-1
	GAREM1	ENST00000399218.8	TSL:2	c.262+2872G>A		intron	N/A	ENSP00000382165.3	Q9H706-3
	GAREM1	ENST00000952372.1		c.262+2872G>A		intron	N/A	ENSP00000622431.1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20220 AN: 151704 Hom.: 1557 Cov.: 31

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.0527

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0981

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0573

Gnomad NFE AF: 0.0961

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.134 AC: 20303 AN: 151822 Hom.: 1575 Cov.: 31 AF XY: 0.134 AC XY: 9970 AN XY: 74182

African (AFR) AF: 0.212 AC: 8767 AN: 41364

American (AMR) AF: 0.105 AC: 1604 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0981 AC: 340 AN: 3466

East Asian (EAS) AF: 0.171 AC: 879 AN: 5150

South Asian (SAS) AF: 0.117 AC: 564 AN: 4810

European-Finnish (FIN) AF: 0.123 AC: 1297 AN: 10536

Middle Eastern (MID) AF: 0.0514 AC: 15 AN: 292

European-Non Finnish (NFE) AF: 0.0961 AC: 6527 AN: 67934

Other (OTH) AF: 0.125 AC: 262 AN: 2098

Alfa AF: 0.110 Hom.: 2646

Bravo AF: 0.138

Asia WGS AF: 0.171 AC: 594 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.8
DANN	Benign	0.57
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs13381088; hg19: chr18-29969986;