chr15-49332587-G-C

Position:

• chr15-49332587-G-C

Variant summary

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

The NM_152647.3(FAM227B):​c.1350-738C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,130 control chromosomes in the GnomAD database, including 3,712 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 0.22 (3712 hom., cov: 32)
• Consequence: FAM227B NM_152647.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.35

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM227B	NM_152647.3	c.1350-738C>G		intron_variant		ENST00000299338.11	NP_689860.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM227B	ENST00000299338.11	c.1350-738C>G		intron_variant		2	NM_152647.3	ENSP00000299338	P1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32697 AN: 152012 Hom.: 3706 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.0580

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.215 AC: 32738 AN: 152130 Hom.: 3712 Cov.: 32 AF XY: 0.216 AC XY: 16050 AN XY: 74340

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.0581

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.225

Alfa AF: 0.121 Hom.: 232

Bravo AF: 0.206

Asia WGS AF: 0.177 AC: 615 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	0.087
DANN	Benign	0.36

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: rs17476940; hg19: chr15-49624784;