15-49353213-T-C

Position:

• chr15-49353213-T-C

Variant summary

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

The NM_152647.3(FAM227B):​c.1271+14235A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,078 control chromosomes in the GnomAD database, including 6,398 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 0.28 (6398 hom., cov: 31)
• Consequence: FAM227B NM_152647.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.374

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]

FAM227B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM227B	NM_152647.3	c.1271+14235A>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.1271+14235A>G		intron_variant		2	NM_152647.3	ENSP00000299338.6
GALK2	ENST00000559580.5	c.449-14278T>C		intron_variant		5		ENSP00000453257.1
GALK2	ENST00000558399.5	c.426-14278T>C		intron_variant		5		ENSP00000453252.1
FAM227B	ENST00000559573.3	n.420+18089A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42240 AN: 151960 Hom.: 6400 Cov.: 31

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.329

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

GnomAD4 genome AF: 0.278 AC: 42250 AN: 152078 Hom.: 6398 Cov.: 31 AF XY: 0.280 AC XY: 20804 AN XY: 74330

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.401

Gnomad4 ASJ AF: 0.266

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.305

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.327

Alfa AF: 0.267 Hom.: 669

Bravo AF: 0.289

Asia WGS AF: 0.335 AC: 1169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.4
DANN	Benign	0.71

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: rs6493364; hg19: chr15-49645410;