15-49533326-T-C

Position:

• chr15-49533326-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.874+8354A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 151,730 control chromosomes in the GnomAD database, including 35,948 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 0.68 (35948 hom., cov: 31)
• Consequence: FAM227B NM_152647.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.01

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.07).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM227B	NM_152647.3	c.874+8354A>G		intron_variant		ENST00000299338.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM227B	ENST00000299338.11	c.874+8354A>G		intron_variant		2	NM_152647.3	P1
FAM227B	ENST00000561064.5	c.772+8354A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.685 AC: 103790 AN: 151612 Hom.: 35925 Cov.: 31

Gnomad AFR AF: 0.579

Gnomad AMI AF: 0.771

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.724

Gnomad EAS AF: 0.925

Gnomad SAS AF: 0.679

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.713

Gnomad OTH AF: 0.691

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

GnomAD4 genome AF: 0.684 AC: 103855 AN: 151730 Hom.: 35948 Cov.: 31 AF XY: 0.684 AC XY: 50739 AN XY: 74140

Gnomad4 AFR AF: 0.578

Gnomad4 AMR AF: 0.766

Gnomad4 ASJ AF: 0.724

Gnomad4 EAS AF: 0.925

Gnomad4 SAS AF: 0.680

Gnomad4 FIN AF: 0.659

Gnomad4 NFE AF: 0.713

Gnomad4 OTH AF: 0.687

Alfa AF: 0.689 Hom.: 8243

Bravo AF: 0.692

Asia WGS AF: 0.745 AC: 2595 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.41
DANN	Benign	0.38

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: rs1354920; hg19: chr15-49825523;