rs12591300

Positions:

• chr15-49412544-G-A

Variant summary

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

The NM_152647.3(FAM227B):​c.1013-41145C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 151,572 control chromosomes in the GnomAD database, including 6,038 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 0.26 (6038 hom., cov: 31)
• Consequence: FAM227B NM_152647.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.514

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM227B	NM_152647.3	c.1013-41145C>T		intron_variant		ENST00000299338.11	NP_689860.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM227B	ENST00000299338.11	c.1013-41145C>T		intron_variant		2	NM_152647.3	ENSP00000299338	P1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 38935 AN: 151454 Hom.: 6036 Cov.: 31

Gnomad AFR AF: 0.0840

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.257 AC: 38918 AN: 151572 Hom.: 6038 Cov.: 31 AF XY: 0.255 AC XY: 18891 AN XY: 74030

Gnomad4 AFR AF: 0.0838

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.385

Gnomad4 EAS AF: 0.187

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.353

Gnomad4 OTH AF: 0.271

Alfa AF: 0.317 Hom.: 4127

Bravo AF: 0.245

Asia WGS AF: 0.174 AC: 605 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.91

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: rs12591300; hg19: chr15-49704741;