15-49471768-C-T

Position:

• chr15-49471768-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+36443G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 151,632 control chromosomes in the GnomAD database, including 9,479 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 0.34 (9479 hom., cov: 30)
• Consequence: FAM227B NM_152647.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.18

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]

FGF7 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM227B	NM_152647.3	c.1012+36443G>A		intron_variant		ENST00000299338.11	NP_689860.2
FGF7	NM_002009.4	c.287-11383C>T		intron_variant		ENST00000267843.9	NP_002000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM227B	ENST00000299338.11	c.1012+36443G>A		intron_variant		2	NM_152647.3	ENSP00000299338.6
FGF7	ENST00000267843.9	c.287-11383C>T		intron_variant		1	NM_002009.4	ENSP00000267843.4

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50758 AN: 151514 Hom.: 9463 Cov.: 30

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.335 AC: 50823 AN: 151632 Hom.: 9479 Cov.: 30 AF XY: 0.334 AC XY: 24718 AN XY: 74052

Gnomad4 AFR AF: 0.487

Gnomad4 AMR AF: 0.380

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.380

Gnomad4 SAS AF: 0.308

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.332

Alfa AF: 0.294 Hom.: 1131

Bravo AF: 0.354

Asia WGS AF: 0.337 AC: 1172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.031
DANN	Benign	0.48

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: rs2899433; hg19: chr15-49763965;