chr1-108727780-G-A

Position:

• chr1-108727780-G-A

Variant summary

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

The NM_001144937.3(FNDC7):​c.1112-28G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 1,610,268 control chromosomes in the GnomAD database, including 172,673 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 0.40 (13176 hom., cov: 30)
  • Exomes 𝑓: 0.46 (159497 hom.)
• Consequence: FNDC7 NM_001144937.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650

Genes affected

FNDC7 (HGNC:26668): (fibronectin type III domain containing 7) Predicted to be located in extracellular region. [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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FNDC7	NM_001144937.3	c.1112-28G>A		intron_variant		ENST00000370017.9	NP_001138409.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FNDC7	ENST00000370017.9	c.1112-28G>A		intron_variant		5	NM_001144937.3	ENSP00000359034.3
FNDC7	ENST00000445274.1	c.437-28G>A		intron_variant		1		ENSP00000405986.1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61020 AN: 151724 Hom.: 13169 Cov.: 30

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.385

GnomAD3 exomes AF: 0.428 AC: 106271 AN: 248426 Hom.: 24021 AF XY: 0.437 AC XY: 58543 AN XY: 134118

Gnomad AFR exome AF: 0.267

Gnomad AMR exome AF: 0.357

Gnomad ASJ exome AF: 0.444

Gnomad EAS exome AF: 0.188

Gnomad SAS exome AF: 0.461

Gnomad FIN exome AF: 0.504

Gnomad NFE exome AF: 0.486

Gnomad OTH exome AF: 0.441

GnomAD4 exome AF: 0.463 AC: 675394 AN: 1458428 Hom.: 159497 Cov.: 44 AF XY: 0.464 AC XY: 336676 AN XY: 725348

Gnomad4 AFR exome AF: 0.260

Gnomad4 AMR exome AF: 0.355

Gnomad4 ASJ exome AF: 0.445

Gnomad4 EAS exome AF: 0.192

Gnomad4 SAS exome AF: 0.460

Gnomad4 FIN exome AF: 0.505

Gnomad4 NFE exome AF: 0.483

Gnomad4 OTH exome AF: 0.439

GnomAD4 genome AF: 0.402 AC: 61041 AN: 151840 Hom.: 13176 Cov.: 30 AF XY: 0.402 AC XY: 29821 AN XY: 74188

Gnomad4 AFR AF: 0.276

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.457

Gnomad4 FIN AF: 0.508

Gnomad4 NFE AF: 0.487

Gnomad4 OTH AF: 0.381

Alfa AF: 0.462 Hom.: 28536

Bravo AF: 0.383

Asia WGS AF: 0.307 AC: 1073 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.7
DANN	Benign	0.51

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: rs10494096; hg19: chr1-109270402; COSMIC: COSV54750861;