NM_001242409.2:c.122-30445C>G

Variant names:

• chr18-32423480-G-C
• rs10502598
• NM_001242409.2:c.122-30445C>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.122-30445C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.046 in 152,240 control chromosomes in the GnomAD database, including 470 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 0.046 (470 hom., cov: 32)
• Consequence: GAREM1 NM_001242409.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.592
• Publications: 0 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAREM1	NM_001242409.2	c.122-30445C>G		intron_variant	Intron 1 of 5	ENST00000269209.7	NP_001229338.1
GAREM1	NM_022751.3	c.122-30445C>G		intron_variant	Intron 1 of 5		NP_073588.1
GAREM1	XM_017025919.2	c.122-30445C>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.122-30445C>G		intron_variant	Intron 1 of 5	1	NM_001242409.2	ENSP00000269209.6
GAREM1	ENST00000399218.8	c.122-30445C>G		intron_variant	Intron 1 of 5	2		ENSP00000382165.3

Frequencies

GnomAD3 genomes AF: 0.0459 AC: 6984 AN: 152122 Hom.: 470 Cov.: 32

Gnomad AFR AF: 0.0312

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0747

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.0416

Gnomad FIN AF: 0.0914

Gnomad MID AF: 0.0255

Gnomad NFE AF: 0.0222

Gnomad OTH AF: 0.0445

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

GnomAD4 genome AF: 0.0460 AC: 7002 AN: 152240 Hom.: 470 Cov.: 32 AF XY: 0.0499 AC XY: 3711 AN XY: 74430

African (AFR) AF: 0.0313 AC: 1299 AN: 41534

American (AMR) AF: 0.0752 AC: 1151 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0219 AC: 76 AN: 3466

East Asian (EAS) AF: 0.320 AC: 1658 AN: 5176

South Asian (SAS) AF: 0.0425 AC: 205 AN: 4824

European-Finnish (FIN) AF: 0.0914 AC: 969 AN: 10596

Middle Eastern (MID) AF: 0.0205 AC: 6 AN: 292

European-Non Finnish (NFE) AF: 0.0222 AC: 1512 AN: 68026

Other (OTH) AF: 0.0459 AC: 97 AN: 2114

Alfa AF: 0.0300 Hom.: 26

Bravo AF: 0.0485

Asia WGS AF: 0.156 AC: 541 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.59
PhyloP100		0.59
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: rs10502598; hg19: chr18-30003443;