rs3786310

Variant names:

• chr18-32392761-A-G
• rs3786310
• NM_001242409.2:c.262+134T>C

Your query was ambiguous. Multiple possible variants found:

• chr18-32392761-A-G
• chr18-32392761-A-T

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+134T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 903,690 control chromosomes in the GnomAD database, including 6,154 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: 32)
  • Exomes 𝑓: 0.11 (4579 hom.)
• Consequence: GAREM1 NM_001242409.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.285
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAREM1	NM_001242409.2	c.262+134T>C		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.262+134T>C		intron_variant	Intron 2 of 5	1	NM_001242409.2	ENSP00000269209.6
GAREM1	ENST00000399218.8	c.262+134T>C		intron_variant	Intron 2 of 5	2		ENSP00000382165.3

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20256 AN: 152108 Hom.: 1557 Cov.: 32

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0980

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0960

Gnomad OTH AF: 0.119

GnomAD4 exome AF: 0.106 AC: 79375 AN: 751464 Hom.: 4579 AF XY: 0.105 AC XY: 39516 AN XY: 378016

African (AFR) AF: 0.207 AC: 3939 AN: 19016

American (AMR) AF: 0.105 AC: 2172 AN: 20668

Ashkenazi Jewish (ASJ) AF: 0.0999 AC: 1487 AN: 14880

East Asian (EAS) AF: 0.184 AC: 6215 AN: 33834

South Asian (SAS) AF: 0.112 AC: 4577 AN: 40784

European-Finnish (FIN) AF: 0.116 AC: 4833 AN: 41812

Middle Eastern (MID) AF: 0.0948 AC: 367 AN: 3872

European-Non Finnish (NFE) AF: 0.0957 AC: 51790 AN: 541256

Other (OTH) AF: 0.113 AC: 3995 AN: 35342

GnomAD4 genome AF: 0.134 AC: 20339 AN: 152226 Hom.: 1575 Cov.: 32 AF XY: 0.134 AC XY: 10009 AN XY: 74442

African (AFR) AF: 0.212 AC: 8786 AN: 41526

American (AMR) AF: 0.105 AC: 1602 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0980 AC: 340 AN: 3470

East Asian (EAS) AF: 0.171 AC: 885 AN: 5182

South Asian (SAS) AF: 0.117 AC: 564 AN: 4820

European-Finnish (FIN) AF: 0.123 AC: 1305 AN: 10606

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0960 AC: 6530 AN: 68000

Other (OTH) AF: 0.125 AC: 264 AN: 2114

Alfa AF: 0.0934 Hom.: 454

Bravo AF: 0.138

Asia WGS AF: 0.171 AC: 592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.48
PhyloP100		-0.28
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: rs3786310; hg19: chr18-29972724; COSMIC: COSV52508456;