18-32320734-G-T

Variant names:

• chr18-32320734-G-T
• rs667604
• NM_001242409.2:c.263-10411C>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.263-10411C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0888 in 152,060 control chromosomes in the GnomAD database, including 658 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 0.089 (658 hom., cov: 32)
• Consequence: GAREM1 NM_001242409.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07
• Publications: 3 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=-0.7).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAREM1	NM_001242409.2	c.263-10411C>A		intron_variant	Intron 2 of 5	ENST00000269209.7	NP_001229338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAREM1	ENST00000269209.7	c.263-10411C>A		intron_variant	Intron 2 of 5	1	NM_001242409.2	ENSP00000269209.6
GAREM1	ENST00000399218.8	c.263-10411C>A		intron_variant	Intron 2 of 5	2		ENSP00000382165.3
GAREM1	ENST00000578619.1	n.92-10411C>A		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes AF: 0.0888 AC: 13489 AN: 151942 Hom.: 657 Cov.: 32

Gnomad AFR AF: 0.0637

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0683

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.0131

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0938

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0900

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

GnomAD4 genome AF: 0.0888 AC: 13502 AN: 152060 Hom.: 658 Cov.: 32 AF XY: 0.0864 AC XY: 6421 AN XY: 74332

African (AFR) AF: 0.0637 AC: 2644 AN: 41476

American (AMR) AF: 0.0682 AC: 1040 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 442 AN: 3468

East Asian (EAS) AF: 0.0131 AC: 68 AN: 5182

South Asian (SAS) AF: 0.121 AC: 583 AN: 4816

European-Finnish (FIN) AF: 0.0938 AC: 992 AN: 10578

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7440 AN: 67966

Other (OTH) AF: 0.0929 AC: 196 AN: 2110

Alfa AF: 0.0513 Hom.: 46

Bravo AF: 0.0845

Asia WGS AF: 0.0830 AC: 288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	11
DANN	Benign	0.75
PhyloP100		1.1
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: rs667604; hg19: chr18-29900697;