rs12439479

chr15-49442646-A-Gchr15-49442646-A-T

Variant summary

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

The NM_152647.3(FAM227B):c.1012+65565T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 151,554 control chromosomes in the GnomAD database, including 5,318 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 (5318 hom., cov: 32)
• Consequence: FAM227B NM_152647.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720

Genes affected

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]

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGF7	NM_002009.4	c.286+18063A>G		intron_variant		ENST00000267843.9
FAM227B	NM_152647.3	c.1012+65565T>C		intron_variant		ENST00000299338.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGF7	ENST00000267843.9	c.286+18063A>G		intron_variant		1	NM_002009.4	P1
FAM227B	ENST00000299338.11	c.1012+65565T>C		intron_variant		2	NM_152647.3	P1

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38770 AN: 151436 Hom.: 5314 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.256 AC: 38793 AN: 151554 Hom.: 5318 Cov.: 32 AF XY: 0.259 AC XY: 19178 AN XY: 74016

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.439

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.245

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.292

Alfa AF: 0.241 Hom.: 542

Bravo AF: 0.267

Asia WGS AF: 0.327 AC: 1138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.9
Dann	Benign	0.33

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: rs12439479; hg19: chr15-49734843;