15-49521146-T-C

Variant names:

• chr15-49521146-T-C
• rs17480434
• NM_152647.3:c.875-12798A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152647.3(FAM227B):​c.875-12798A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,162 control chromosomes in the GnomAD database, including 3,174 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 0.18 (3174 hom., cov: 32)
• Consequence: FAM227B NM_152647.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.206
• Publications: 2 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM227B	NM_152647.3	c.875-12798A>G		intron_variant	Intron 10 of 15	ENST00000299338.11	NP_689860.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM227B	ENST00000299338.11	c.875-12798A>G		intron_variant	Intron 10 of 15	2	NM_152647.3	ENSP00000299338.6
FAM227B	ENST00000561064.5	c.773-12798A>G		intron_variant	Intron 9 of 10	1		ENSP00000453028.1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27891 AN: 152042 Hom.: 3177 Cov.: 32

Gnomad AFR AF: 0.0603

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.00463

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.186

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.183 AC: 27877 AN: 152162 Hom.: 3174 Cov.: 32 AF XY: 0.185 AC XY: 13782 AN XY: 74372

African (AFR) AF: 0.0601 AC: 2499 AN: 41558

American (AMR) AF: 0.172 AC: 2630 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 887 AN: 3468

East Asian (EAS) AF: 0.00484 AC: 25 AN: 5168

South Asian (SAS) AF: 0.174 AC: 838 AN: 4820

European-Finnish (FIN) AF: 0.316 AC: 3339 AN: 10576

Middle Eastern (MID) AF: 0.178 AC: 52 AN: 292

European-Non Finnish (NFE) AF: 0.250 AC: 16980 AN: 67980

Other (OTH) AF: 0.199 AC: 419 AN: 2110

Alfa AF: 0.181 Hom.: 1008

Bravo AF: 0.167

Asia WGS AF: 0.0770 AC: 267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.6
DANN	Benign	0.72
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17480434; hg19: chr15-49813343;