rs704795

Positions:

• chr2-27493627-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000264703.4(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 ENST00000264703.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.780

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FNDC4	NM_022823.3	c.455-149C>T		intron_variant		ENST00000264703.4	NP_073734.1
FNDC4	XM_005264499.5	c.455-149C>T		intron_variant			XP_005264556.1
FNDC4	XM_047445471.1	c.455-149C>T		intron_variant			XP_047301427.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FNDC4	ENST00000264703.4	c.455-149C>T		intron_variant		1	NM_022823.3	ENSP00000264703	P1
FNDC4	ENST00000476197.1	n.588-149C>T		intron_variant, non_coding_transcript_variant		2
FNDC4	ENST00000491414.5	n.980-149C>T		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR exome AF: 0.610

Gnomad4 AMR exome AF: 0.537

Gnomad4 ASJ exome AF: 0.334

Gnomad4 EAS exome AF: 0.129

Gnomad4 SAS exome AF: 0.413

Gnomad4 FIN exome AF: 0.429

Gnomad4 NFE exome AF: 0.370

Gnomad4 OTH exome AF: 0.384

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

Gnomad4 AFR AF: 0.615

Gnomad4 AMR AF: 0.466

Gnomad4 ASJ AF: 0.339

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.424

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.383

Gnomad4 OTH AF: 0.402

Alfa AF: 0.383 Hom.: 11041

Bravo AF: 0.458

Asia WGS AF: 0.353 AC: 1228 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.68
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs704795; hg19: chr2-27716494; COSMIC: COSV53020929; COSMIC: COSV53020929;