rs2707496

Variant names:

• chr7-121370844-C-T
• rs2707496
• NM_014888.3:c.272+456G>A

Variant summary

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

The NM_014888.3(FAM3C):​c.272+456G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,098 control chromosomes in the GnomAD database, including 5,949 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 0.26 (5949 hom., cov: 32)
• Consequence: FAM3C NM_014888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.94
• Publications: 4 publications found

Genes affected

FAM3C (HGNC:18664): (FAM3 metabolism regulating signaling molecule C) This gene is a member of the family with sequence similarity 3 (FAM3) family and encodes a secreted protein with a GG domain. A change in expression of this protein has been noted in pancreatic cancer-derived cells. [provided by RefSeq, Mar 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM3C	NM_014888.3	c.272+456G>A		intron_variant	Intron 5 of 9	ENST00000359943.8	NP_055703.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM3C	ENST00000359943.8	c.272+456G>A		intron_variant	Intron 5 of 9	1	NM_014888.3	ENSP00000353025.3
FAM3C	ENST00000850865.1	c.272+456G>A		intron_variant	Intron 5 of 9			ENSP00000520951.1
FAM3C	ENST00000412653.5	c.272+456G>A		intron_variant	Intron 5 of 7	4		ENSP00000408636.1
FAM3C	ENST00000426156.1	c.182+456G>A		intron_variant	Intron 6 of 8	5		ENSP00000414940.1

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38787 AN: 151980 Hom.: 5923 Cov.: 32

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.0402

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.255 AC: 38853 AN: 152098 Hom.: 5949 Cov.: 32 AF XY: 0.251 AC XY: 18643 AN XY: 74358

African (AFR) AF: 0.438 AC: 18164 AN: 41456

American (AMR) AF: 0.174 AC: 2653 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 534 AN: 3466

East Asian (EAS) AF: 0.0401 AC: 208 AN: 5182

South Asian (SAS) AF: 0.211 AC: 1013 AN: 4812

European-Finnish (FIN) AF: 0.187 AC: 1978 AN: 10590

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13585 AN: 67986

Other (OTH) AF: 0.230 AC: 486 AN: 2112

Alfa AF: 0.249 Hom.: 981

Bravo AF: 0.260

Asia WGS AF: 0.140 AC: 486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.0050
DANN	Benign	0.72
PhyloP100		-2.9
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: rs2707496; hg19: chr7-121010898;