rs704795

Variant names:

• chr2-27493627-G-A
• rs704795
• NM_022823.3:c.455-149C>T

Variant summary

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

The NM_022823.3(FNDC4):​c.455-149C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 727,048 control chromosomes in the GnomAD database, including 60,546 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 0.45 (16460 hom., cov: 32)
  • Exomes 𝑓: 0.38 (44086 hom.)
• Consequence: FNDC4 NM_022823.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.780
• Publications: 29 publications found

Genes affected

FNDC4 (HGNC:20239): (fibronectin type III domain containing 4) Involved in response to transforming growth factor beta. Predicted to be located in endoplasmic reticulum and extracellular space. Predicted to be active in extracellular region and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022823.3. 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
	FNDC4	NM_022823.3	MANE Select	c.455-149C>T		intron	N/A	NP_073734.1	Q9H6D8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FNDC4	ENST00000264703.4	TSL:1 MANE Select	c.455-149C>T		intron	N/A	ENSP00000264703.3	Q9H6D8
	FNDC4	ENST00000934125.1		c.455-149C>T		intron	N/A	ENSP00000604184.1
	FNDC4	ENST00000951222.1		c.455-149C>T		intron	N/A	ENSP00000621281.1

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68241 AN: 151934 Hom.: 16418 Cov.: 32

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.398

GnomAD4 exome AF: 0.378 AC: 217139 AN: 574996 Hom.: 44086 AF XY: 0.377 AC XY: 115076 AN XY: 304842

African (AFR) AF: 0.610 AC: 9389 AN: 15394

American (AMR) AF: 0.537 AC: 14914 AN: 27778

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 5291 AN: 15848

East Asian (EAS) AF: 0.129 AC: 4383 AN: 34034

South Asian (SAS) AF: 0.413 AC: 22908 AN: 55404

European-Finnish (FIN) AF: 0.429 AC: 16728 AN: 39006

Middle Eastern (MID) AF: 0.319 AC: 764 AN: 2392

European-Non Finnish (NFE) AF: 0.370 AC: 131042 AN: 354582

Other (OTH) AF: 0.384 AC: 11720 AN: 30558

GnomAD4 genome AF: 0.449 AC: 68345 AN: 152052 Hom.: 16460 Cov.: 32 AF XY: 0.449 AC XY: 33338 AN XY: 74326

African (AFR) AF: 0.615 AC: 25516 AN: 41462

American (AMR) AF: 0.466 AC: 7127 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1175 AN: 3468

East Asian (EAS) AF: 0.151 AC: 782 AN: 5178

South Asian (SAS) AF: 0.424 AC: 2037 AN: 4808

European-Finnish (FIN) AF: 0.430 AC: 4543 AN: 10574

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 26007 AN: 67968

Other (OTH) AF: 0.402 AC: 847 AN: 2106

Alfa AF: 0.397 Hom.: 15709

Bravo AF: 0.458

Asia WGS AF: 0.353 AC: 1228 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.68
DANN	Benign	0.75
PhyloP100		-0.78
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: rs704795; hg19: chr2-27716494; COSMIC: COSV53020929; COSMIC: COSV53020929;