rs12595692

Positions:

• chr15-49464911-C-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+43300G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 151,916 control chromosomes in the GnomAD database, including 5,768 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 0.25 (5768 hom., cov: 31)
• Consequence: FAM227B NM_152647.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGF7	NM_002009.4	c.287-18240C>T		intron_variant		ENST00000267843.9	NP_002000.1
FAM227B	NM_152647.3	c.1012+43300G>A		intron_variant		ENST00000299338.11	NP_689860.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGF7	ENST00000267843.9	c.287-18240C>T		intron_variant		1	NM_002009.4	ENSP00000267843	P1
FAM227B	ENST00000299338.11	c.1012+43300G>A		intron_variant		2	NM_152647.3	ENSP00000299338	P1

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38655 AN: 151800 Hom.: 5767 Cov.: 31

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.254 AC: 38642 AN: 151916 Hom.: 5768 Cov.: 31 AF XY: 0.251 AC XY: 18652 AN XY: 74240

Gnomad4 AFR AF: 0.0999

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.354

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.269

Alfa AF: 0.289 Hom.: 889

Bravo AF: 0.244

Asia WGS AF: 0.176 AC: 612 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.5
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12595692; hg19: chr15-49757108;