rs12595692

Variant names:

• chr15-49464911-C-T
• rs12595692
• NM_152647.3:c.1012+43300G>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+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
• Publications: 2 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.343 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM227B	NM_152647.3	MANE Select	c.1012+43300G>A		intron	N/A	NP_689860.2	Q96M60-1
	FGF7	NM_002009.4	MANE Select	c.287-18240C>T		intron	N/A	NP_002000.1	P21781-1
	FAM227B	NM_001330293.2		c.911-42197G>A		intron	N/A	NP_001317222.1	Q96M60-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM227B	ENST00000299338.11	TSL:2 MANE Select	c.1012+43300G>A		intron	N/A	ENSP00000299338.6	Q96M60-1
	FGF7	ENST00000267843.9	TSL:1 MANE Select	c.287-18240C>T		intron	N/A	ENSP00000267843.4	P21781-1
	FAM227B	ENST00000561064.5	TSL:1	c.911-42197G>A		intron	N/A	ENSP00000453028.1	Q96M60-2

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

African (AFR) AF: 0.0999 AC: 4142 AN: 41450

American (AMR) AF: 0.247 AC: 3775 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1229 AN: 3468

East Asian (EAS) AF: 0.183 AC: 945 AN: 5152

South Asian (SAS) AF: 0.199 AC: 959 AN: 4808

European-Finnish (FIN) AF: 0.286 AC: 3008 AN: 10514

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.347 AC: 23545 AN: 67948

Other (OTH) AF: 0.269 AC: 568 AN: 2110

Alfa AF: 0.282 Hom.: 891

Bravo AF: 0.244

Asia WGS AF: 0.176 AC: 612 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.5
DANN	Benign	0.53
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12595692; hg19: chr15-49757108;