rs10519227

Positions:

• chr15-49454167-T-A

Variant summary

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

The NM_152647.3(FAM227B):​c.1012+54044A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 151,984 control chromosomes in the GnomAD database, including 3,273 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 0.20 (3273 hom., cov: 32)
• Consequence: FAM227B NM_152647.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.143

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGF7	NM_002009.4	c.287-28984T>A		intron_variant		ENST00000267843.9	NP_002000.1
FAM227B	NM_152647.3	c.1012+54044A>T		intron_variant		ENST00000299338.11	NP_689860.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGF7	ENST00000267843.9	c.287-28984T>A		intron_variant		1	NM_002009.4	ENSP00000267843	P1
FAM227B	ENST00000299338.11	c.1012+54044A>T		intron_variant		2	NM_152647.3	ENSP00000299338	P1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30278 AN: 151866 Hom.: 3272 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.0814

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.199 AC: 30291 AN: 151984 Hom.: 3273 Cov.: 32 AF XY: 0.204 AC XY: 15125 AN XY: 74268

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.0818

Gnomad4 SAS AF: 0.330

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.233

Gnomad4 OTH AF: 0.216

Alfa AF: 0.219 Hom.: 465

Bravo AF: 0.185

Asia WGS AF: 0.205 AC: 712 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.79

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: rs10519227; hg19: chr15-49746364;