rs2163095

Positions:

• chr15-49349690-A-G

Variant summary

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

The NM_152647.3(FAM227B):​c.1272-14194T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 151,876 control chromosomes in the GnomAD database, including 13,524 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 0.42 (13524 hom., cov: 31)
• Consequence: FAM227B NM_152647.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.197

Genes affected

FAM227B (HGNC:26543): (family with sequence similarity 227 member B)

GALK2 (HGNC:4119): (galactokinase 2) This gene encodes a highly efficient N-acetylgalactosamine (GalNAc) kinase, which has galactokinase activity when galactose is present at high concentrations. The encoded protein is a member of the GHMP kinase family. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM227B	NM_152647.3	c.1272-14194T>C		intron_variant		ENST00000299338.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM227B	ENST00000299338.11	c.1272-14194T>C		intron_variant		2	NM_152647.3	P1
GALK2	ENST00000558399.5	c.427-17801A>G		intron_variant		5
GALK2	ENST00000559580.5	c.449-17801A>G		intron_variant		5
FAM227B	ENST00000559573.3	n.421-17841T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63733 AN: 151756 Hom.: 13517 Cov.: 31

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.380

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

GnomAD4 genome AF: 0.420 AC: 63762 AN: 151876 Hom.: 13524 Cov.: 31 AF XY: 0.418 AC XY: 30990 AN XY: 74220

Gnomad4 AFR AF: 0.450

Gnomad4 AMR AF: 0.343

Gnomad4 ASJ AF: 0.464

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.401

Gnomad4 FIN AF: 0.393

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.375

Alfa AF: 0.433 Hom.: 1823

Bravo AF: 0.416

Asia WGS AF: 0.403 AC: 1402 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	14
DANN	Benign	0.90

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: rs2163095; hg19: chr15-49641887;