18-32446429-T-C

Variant names:

• chr18-32446429-T-C
• rs11662168
• NM_001242409.2:c.121+23879A>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.121+23879A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,104 control chromosomes in the GnomAD database, including 2,001 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 0.15 (2001 hom., cov: 33)
• Consequence: GAREM1 NM_001242409.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAREM1	NM_001242409.2	c.121+23879A>G		intron_variant	Intron 1 of 5	ENST00000269209.7	NP_001229338.1
GAREM1	NM_022751.3	c.121+23879A>G		intron_variant	Intron 1 of 5		NP_073588.1
GAREM1	XM_017025919.2	c.121+23879A>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.121+23879A>G		intron_variant	Intron 1 of 5	1	NM_001242409.2	ENSP00000269209.6
GAREM1	ENST00000399218.8	c.121+23879A>G		intron_variant	Intron 1 of 5	2		ENSP00000382165.3

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22258 AN: 151986 Hom.: 1980 Cov.: 33

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.147 AC: 22334 AN: 152104 Hom.: 2001 Cov.: 33 AF XY: 0.149 AC XY: 11076 AN XY: 74334

African (AFR) AF: 0.194 AC: 8053 AN: 41498

American (AMR) AF: 0.152 AC: 2325 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 409 AN: 3464

East Asian (EAS) AF: 0.397 AC: 2047 AN: 5152

South Asian (SAS) AF: 0.147 AC: 709 AN: 4816

European-Finnish (FIN) AF: 0.139 AC: 1476 AN: 10584

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6920 AN: 67990

Other (OTH) AF: 0.152 AC: 322 AN: 2116

Alfa AF: 0.109 Hom.: 1333

Bravo AF: 0.153

Asia WGS AF: 0.284 AC: 986 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.033
DANN	Benign	0.48
PhyloP100		-1.3
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: rs11662168; hg19: chr18-30026392;