18-32147477-T-C

Variant names:

• chr18-32147477-T-C
• rs12457723
• ENST00000583696.1:c.64-11017A>G

Variant summary

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

The ENST00000583696.1(GAREM1):​c.64-11017A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 152,036 control chromosomes in the GnomAD database, including 10,636 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 0.34 (10636 hom., cov: 32)
• Consequence: GAREM1 ENST00000583696.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.275
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAREM1	ENST00000583696.1	c.64-11017A>G		intron_variant	Intron 1 of 2	3		ENSP00000464185.1

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51022 AN: 151918 Hom.: 10631 Cov.: 32

Gnomad AFR AF: 0.0833

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.365

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.336 AC: 51026 AN: 152036 Hom.: 10636 Cov.: 32 AF XY: 0.340 AC XY: 25245 AN XY: 74326

African (AFR) AF: 0.0830 AC: 3446 AN: 41528

American (AMR) AF: 0.501 AC: 7652 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1423 AN: 3464

East Asian (EAS) AF: 0.408 AC: 2106 AN: 5158

South Asian (SAS) AF: 0.347 AC: 1671 AN: 4816

European-Finnish (FIN) AF: 0.464 AC: 4900 AN: 10562

Middle Eastern (MID) AF: 0.359 AC: 104 AN: 290

European-Non Finnish (NFE) AF: 0.421 AC: 28583 AN: 67924

Other (OTH) AF: 0.367 AC: 776 AN: 2116

Alfa AF: 0.233 Hom.: 615

Bravo AF: 0.330

Asia WGS AF: 0.386 AC: 1339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.2
DANN	Benign	0.80
PhyloP100		0.28

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12457723; hg19: chr18-29727440;