rs58263042

Variant names:

• chr18-32399612-G-C
• rs58263042
• NM_001242409.2:c.122-6577C>G

Variant summary

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

The NM_001242409.2(GAREM1):​c.122-6577C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 151,832 control chromosomes in the GnomAD database, including 5,504 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 0.24 (5504 hom., cov: 32)
• Consequence: GAREM1 NM_001242409.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95
• Publications: 4 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAREM1	NM_001242409.2	c.122-6577C>G		intron_variant	Intron 1 of 5	ENST00000269209.7	NP_001229338.1
GAREM1	NM_022751.3	c.122-6577C>G		intron_variant	Intron 1 of 5		NP_073588.1
GAREM1	XM_024451234.2	c.-245-6577C>G		intron_variant	Intron 1 of 5		XP_024307002.1
GAREM1	XM_017025919.2	c.122-6577C>G		intron_variant	Intron 1 of 5		XP_016881408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAREM1	ENST00000269209.7	c.122-6577C>G		intron_variant	Intron 1 of 5	1	NM_001242409.2	ENSP00000269209.6
GAREM1	ENST00000399218.8	c.122-6577C>G		intron_variant	Intron 1 of 5	2		ENSP00000382165.3

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36208 AN: 151716 Hom.: 5458 Cov.: 32

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.239 AC: 36325 AN: 151832 Hom.: 5504 Cov.: 32 AF XY: 0.239 AC XY: 17730 AN XY: 74198

African (AFR) AF: 0.434 AC: 17939 AN: 41352

American (AMR) AF: 0.176 AC: 2678 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 454 AN: 3470

East Asian (EAS) AF: 0.190 AC: 983 AN: 5166

South Asian (SAS) AF: 0.177 AC: 850 AN: 4806

European-Finnish (FIN) AF: 0.211 AC: 2220 AN: 10544

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10504 AN: 67926

Other (OTH) AF: 0.221 AC: 465 AN: 2108

Alfa AF: 0.210 Hom.: 522

Bravo AF: 0.247

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.60
DANN	Benign	0.42
PhyloP100		-1.9
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: rs58263042; hg19: chr18-29979575;