rs4338740

Positions:

• chr15-49443100-T-C

Variant summary

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

The NM_152647.3(FAM227B):​c.1012+65111A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 151,566 control chromosomes in the GnomAD database, including 4,019 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 0.22 (4019 hom., cov: 32)
• Consequence: FAM227B NM_152647.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM227B	NM_152647.3	c.1012+65111A>G		intron_variant		ENST00000299338.11	NP_689860.2
FGF7	NM_002009.4	c.286+18517T>C		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+65111A>G		intron_variant		2	NM_152647.3	ENSP00000299338.6
FGF7	ENST00000267843.9	c.286+18517T>C		intron_variant		1	NM_002009.4	ENSP00000267843.4

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33305 AN: 151448 Hom.: 4018 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.0854

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.220 AC: 33318 AN: 151566 Hom.: 4019 Cov.: 32 AF XY: 0.224 AC XY: 16601 AN XY: 74024

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.0858

Gnomad4 SAS AF: 0.336

Gnomad4 FIN AF: 0.309

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.227

Alfa AF: 0.257 Hom.: 8404

Bravo AF: 0.204

Asia WGS AF: 0.212 AC: 738 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.25
DANN	Benign	0.73

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: rs4338740; hg19: chr15-49735297;