chr15-49445499-A-G

Variant names:

• chr15-49445499-A-G
• rs8031680
• NM_152647.3:c.1012+62712T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152647.3(FAM227B):​c.1012+62712T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.889 in 151,436 control chromosomes in the GnomAD database, including 61,678 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 0.89 (61678 hom., cov: 31)
• Consequence: FAM227B NM_152647.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.142
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.988 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM227B	NM_152647.3	c.1012+62712T>C		intron_variant	Intron 11 of 15	ENST00000299338.11	NP_689860.2
FGF7	NM_002009.4	c.286+20916A>G		intron_variant	Intron 2 of 3	ENST00000267843.9	NP_002000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM227B	ENST00000299338.11	c.1012+62712T>C		intron_variant	Intron 11 of 15	2	NM_152647.3	ENSP00000299338.6
FGF7	ENST00000267843.9	c.286+20916A>G		intron_variant	Intron 2 of 3	1	NM_002009.4	ENSP00000267843.4

Frequencies

GnomAD3 genomes AF: 0.889 AC: 134517 AN: 151318 Hom.: 61652 Cov.: 31

Gnomad AFR AF: 0.635

Gnomad AMI AF: 0.997

Gnomad AMR AF: 0.965

Gnomad ASJ AF: 0.998

Gnomad EAS AF: 0.946

Gnomad SAS AF: 0.915

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.994

Gnomad OTH AF: 0.925

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

GnomAD4 genome AF: 0.889 AC: 134590 AN: 151436 Hom.: 61678 Cov.: 31 AF XY: 0.892 AC XY: 66017 AN XY: 73994

African (AFR) AF: 0.636 AC: 26268 AN: 41324

American (AMR) AF: 0.965 AC: 14614 AN: 15150

Ashkenazi Jewish (ASJ) AF: 0.998 AC: 3454 AN: 3460

East Asian (EAS) AF: 0.946 AC: 4857 AN: 5136

South Asian (SAS) AF: 0.915 AC: 4404 AN: 4812

European-Finnish (FIN) AF: 1.00 AC: 10618 AN: 10620

Middle Eastern (MID) AF: 0.969 AC: 285 AN: 294

European-Non Finnish (NFE) AF: 0.994 AC: 67248 AN: 67622

Other (OTH) AF: 0.918 AC: 1935 AN: 2108

Alfa AF: 0.911 Hom.: 9003

Bravo AF: 0.878

Asia WGS AF: 0.878 AC: 3043 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.8
DANN	Benign	0.61
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8031680; hg19: chr15-49737696;