2-27492549-C-T

Position:

• chr2-27492549-C-T

Variant summary

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

The NM_022823.3(FNDC4):​c.670-71G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 1,585,768 control chromosomes in the GnomAD database, including 119,086 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 0.37 (11012 hom., cov: 31)
  • Exomes 𝑓: 0.38 (108074 hom.)
• Consequence: FNDC4 NM_022823.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.209

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]

FNDC4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FNDC4	NM_022823.3	c.670-71G>A		intron_variant		ENST00000264703.4	NP_073734.1
FNDC4	XM_047445471.1	c.670-71G>A		intron_variant			XP_047301427.1
FNDC4	XM_005264499.5	c.545-71G>A		intron_variant			XP_005264556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FNDC4	ENST00000264703.4	c.670-71G>A		intron_variant		1	NM_022823.3	ENSP00000264703.3
FNDC4	ENST00000491414.5	n.1070-71G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56896 AN: 151834 Hom.: 10991 Cov.: 31

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.350

GnomAD4 exome AF: 0.383 AC: 548733 AN: 1433816 Hom.: 108074 Cov.: 26 AF XY: 0.382 AC XY: 273465 AN XY: 715074

Gnomad4 AFR exome AF: 0.354

Gnomad4 AMR exome AF: 0.538

Gnomad4 ASJ exome AF: 0.337

Gnomad4 EAS exome AF: 0.133

Gnomad4 SAS exome AF: 0.416

Gnomad4 FIN exome AF: 0.432

Gnomad4 NFE exome AF: 0.383

Gnomad4 OTH exome AF: 0.367

GnomAD4 genome AF: 0.375 AC: 56948 AN: 151952 Hom.: 11012 Cov.: 31 AF XY: 0.375 AC XY: 27877 AN XY: 74302

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.437

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.424

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.378

Gnomad4 OTH AF: 0.355

Alfa AF: 0.361 Hom.: 10886

Bravo AF: 0.374

Asia WGS AF: 0.337 AC: 1169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.3
DANN	Benign	0.33
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2303369; hg19: chr2-27715416; COSMIC: COSV53020900; COSMIC: COSV53020900;