rs10519224

Variant names:

• chr15-49427756-A-C
• rs10519224
• NM_152647.3:c.1013-56357T>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.1013-56357T>G 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 151,780 control chromosomes in the GnomAD database, including 7,137 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 (7137 hom., cov: 31)
• Consequence: FAM227B NM_152647.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.579
• Publications: 5 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=-0.86).
• 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.1013-56357T>G		intron_variant	Intron 11 of 15	ENST00000299338.11	NP_689860.2
FGF7	NM_002009.4	c.286+3173A>C		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.1013-56357T>G		intron_variant	Intron 11 of 15	2	NM_152647.3	ENSP00000299338.6
FGF7	ENST00000267843.9	c.286+3173A>C		intron_variant	Intron 2 of 3	1	NM_002009.4	ENSP00000267843.4
FAM227B	ENST00000561064.5	c.911-5042T>G		intron_variant	Intron 10 of 10	1		ENSP00000453028.1
FGF7	ENST00000560979.1	c.112+3173A>C		intron_variant	Intron 2 of 3	3		ENSP00000453980.1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42073 AN: 151662 Hom.: 7136 Cov.: 31

Gnomad AFR AF: 0.0898

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.277 AC: 42056 AN: 151780 Hom.: 7137 Cov.: 31 AF XY: 0.275 AC XY: 20427 AN XY: 74158

African (AFR) AF: 0.0897 AC: 3718 AN: 41454

American (AMR) AF: 0.269 AC: 4085 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1512 AN: 3466

East Asian (EAS) AF: 0.185 AC: 949 AN: 5128

South Asian (SAS) AF: 0.216 AC: 1039 AN: 4820

European-Finnish (FIN) AF: 0.342 AC: 3606 AN: 10552

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

European-Non Finnish (NFE) AF: 0.383 AC: 26004 AN: 67868

Other (OTH) AF: 0.285 AC: 599 AN: 2102

Alfa AF: 0.345 Hom.: 5589

Bravo AF: 0.264

Asia WGS AF: 0.179 AC: 624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.66
DANN	Benign	0.42
PhyloP100		-0.58
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: rs10519224; hg19: chr15-49719953;