rs10519225

Variant names:

• chr15-49428581-G-A
• rs10519225
• NM_152647.3:c.1013-57182C>T

Variant summary

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

The NM_152647.3(FAM227B):​c.1013-57182C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 151,852 control chromosomes in the GnomAD database, including 7,131 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 (7131 hom., cov: 32)
• Consequence: FAM227B NM_152647.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• Publications: 7 publications found

Genes affected

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

FGF7 (HGNC:3685): (fibroblast growth factor 7) The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. This protein is a potent epithelial cell-specific growth factor, whose mitogenic activity is predominantly exhibited in keratinocytes but not in fibroblasts and endothelial cells. Studies of mouse and rat homologs of this gene implicated roles in morphogenesis of epithelium, reepithelialization of wounds, hair development and early lung organogenesis. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM227B	NM_152647.3	c.1013-57182C>T		intron_variant	Intron 11 of 15	ENST00000299338.11	NP_689860.2
FGF7	NM_002009.4	c.286+3998G>A		intron_variant	Intron 2 of 3	ENST00000267843.9	NP_002000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM227B	ENST00000299338.11	c.1013-57182C>T		intron_variant	Intron 11 of 15	2	NM_152647.3	ENSP00000299338.6
FGF7	ENST00000267843.9	c.286+3998G>A		intron_variant	Intron 2 of 3	1	NM_002009.4	ENSP00000267843.4
FAM227B	ENST00000561064.5	c.911-5867C>T		intron_variant	Intron 10 of 10	1		ENSP00000453028.1
FGF7	ENST00000560979.1	c.112+3998G>A		intron_variant	Intron 2 of 3	3		ENSP00000453980.1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42073 AN: 151734 Hom.: 7130 Cov.: 32

Gnomad AFR AF: 0.0899

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.277 AC: 42057 AN: 151852 Hom.: 7131 Cov.: 32 AF XY: 0.275 AC XY: 20434 AN XY: 74206

African (AFR) AF: 0.0898 AC: 3723 AN: 41470

American (AMR) AF: 0.269 AC: 4095 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1513 AN: 3468

East Asian (EAS) AF: 0.184 AC: 942 AN: 5118

South Asian (SAS) AF: 0.215 AC: 1032 AN: 4808

European-Finnish (FIN) AF: 0.342 AC: 3617 AN: 10582

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 26000 AN: 67890

Other (OTH) AF: 0.283 AC: 595 AN: 2100

Alfa AF: 0.341 Hom.: 2277

Bravo AF: 0.264

Asia WGS AF: 0.179 AC: 623 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	18
DANN	Benign	0.66
PhyloP100		1.3
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: rs10519225; hg19: chr15-49720778;