rs12916839

Variant names:

• chr15-49443468-C-T
• rs12916839
• NM_152647.3:c.1012+64743G>A

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+64743G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 151,444 control chromosomes in the GnomAD database, including 5,793 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 (5793 hom., cov: 32)
• Consequence: FAM227B NM_152647.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.702
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152647.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM227B	NM_152647.3	MANE Select	c.1012+64743G>A		intron	N/A	NP_689860.2
	FGF7	NM_002009.4	MANE Select	c.286+18885C>T		intron	N/A	NP_002000.1
	FAM227B	NM_001330293.2		c.911-20754G>A		intron	N/A	NP_001317222.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM227B	ENST00000299338.11	TSL:2 MANE Select	c.1012+64743G>A		intron	N/A	ENSP00000299338.6
	FGF7	ENST00000267843.9	TSL:1 MANE Select	c.286+18885C>T		intron	N/A	ENSP00000267843.4
	FAM227B	ENST00000561064.5	TSL:1	c.911-20754G>A		intron	N/A	ENSP00000453028.1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38146 AN: 151328 Hom.: 5792 Cov.: 32

Gnomad AFR AF: 0.0828

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.252 AC: 38129 AN: 151444 Hom.: 5793 Cov.: 32 AF XY: 0.250 AC XY: 18502 AN XY: 73984

African (AFR) AF: 0.0827 AC: 3425 AN: 41424

American (AMR) AF: 0.255 AC: 3862 AN: 15150

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1340 AN: 3460

East Asian (EAS) AF: 0.185 AC: 948 AN: 5126

South Asian (SAS) AF: 0.203 AC: 978 AN: 4818

European-Finnish (FIN) AF: 0.300 AC: 3166 AN: 10536

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23388 AN: 67626

Other (OTH) AF: 0.269 AC: 565 AN: 2100

Alfa AF: 0.292 Hom.: 903

Bravo AF: 0.241

Asia WGS AF: 0.174 AC: 606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.62
DANN	Benign	0.62
PhyloP100		-0.70
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: rs12916839; hg19: chr15-49735665;