rs12148618

chr15-44322486-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138423.4(GOLM2):c.328-479A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0228 in 152,266 control chromosomes in the GnomAD database, including 59 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 0.023 (59 hom., cov: 32)
• Consequence: GOLM2 NM_138423.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440

Genes affected

GOLM2 (HGNC:24892): (golgi membrane protein 2) The increased expression level of this gene is associated with HER-2/neu proto-oncogene overexpression. Amplification and resulting overexpression of this proto-oncogene are found in approximately 30% of human breast and 20% of human ovarian cancers. Alternatively spliced variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GOLM2	NM_138423.4	c.328-479A>G		intron_variant		ENST00000299957.11
GOLM2	NM_177974.3	c.328-479A>G		intron_variant
GOLM2	NR_157849.2	n.639-479A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GOLM2	ENST00000299957.11	c.328-479A>G		intron_variant		1	NM_138423.4	P3

Frequencies

GnomAD3 genomes AF: 0.0228 AC: 3472 AN: 152146 Hom.: 59 Cov.: 32

Gnomad AFR AF: 0.00543

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0347

Gnomad ASJ AF: 0.0354

Gnomad EAS AF: 0.0654

Gnomad SAS AF: 0.0292

Gnomad FIN AF: 0.0211

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0267

Gnomad OTH AF: 0.0239

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

GnomAD4 genome AF: 0.0228 AC: 3471 AN: 152266 Hom.: 59 Cov.: 32 AF XY: 0.0234 AC XY: 1740 AN XY: 74440

Gnomad4 AFR AF: 0.00541

Gnomad4 AMR AF: 0.0346

Gnomad4 ASJ AF: 0.0354

Gnomad4 EAS AF: 0.0655

Gnomad4 SAS AF: 0.0290

Gnomad4 FIN AF: 0.0211

Gnomad4 NFE AF: 0.0267

Gnomad4 OTH AF: 0.0232

Alfa AF: 0.0265 Hom.: 42

Bravo AF: 0.0245

Asia WGS AF: 0.0460 AC: 160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	1.0
Dann	Benign	0.85

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

Publications

LitVar

Other links and lift over

dbSNP: rs12148618; hg19: chr15-44614684;