chr1-108733446-C-T

Variant names:

• chr1-108733446-C-T
• rs1277017
• NM_001144937.3:c.2054C>T

Variant summary

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

The NM_001144937.3(FNDC7):​c.2054C>T​(p.Pro685Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0046 in 1,613,942 control chromosomes in the GnomAD database, including 301 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P685T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.024 (143 hom., cov: 31)
  • Exomes 𝑓: 0.0026 (158 hom.)
• Consequence: FNDC7 NM_001144937.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25
• Publications: 7 publications found

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

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0024515688).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.08 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144937.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FNDC7	NM_001144937.3	MANE Select	c.2054C>T	p.Pro685Leu	missense	Exon 10 of 13	NP_001138409.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FNDC7	ENST00000370017.9	TSL:5 MANE Select	c.2054C>T	p.Pro685Leu	missense	Exon 10 of 13	ENSP00000359034.3
	FNDC7	ENST00000445274.1	TSL:1	c.1379C>T	p.Pro460Leu	missense	Exon 6 of 8	ENSP00000405986.1
	FNDC7	ENST00000932418.1		c.1541C>T	p.Pro514Leu	missense	Exon 8 of 11	ENSP00000602477.1

Frequencies

GnomAD3 genomes AF: 0.0237 AC: 3605 AN: 151960 Hom.: 143 Cov.: 31

Gnomad AFR AF: 0.0825

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00904

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0115

GnomAD2 exomes AF: 0.00618 AC: 1549 AN: 250616 AF XY: 0.00441

Gnomad AFR exome AF: 0.0829

Gnomad AMR exome AF: 0.00422

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000230

Gnomad OTH exome AF: 0.00375

GnomAD4 exome AF: 0.00261 AC: 3822 AN: 1461864 Hom.: 158 Cov.: 32 AF XY: 0.00224 AC XY: 1631 AN XY: 727236

African (AFR) AF: 0.0879 AC: 2942 AN: 33472

American (AMR) AF: 0.00501 AC: 224 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000336 AC: 29 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00867 AC: 50 AN: 5768

European-Non Finnish (NFE) AF: 0.000185 AC: 206 AN: 1111994

Other (OTH) AF: 0.00614 AC: 371 AN: 60396

GnomAD4 genome AF: 0.0237 AC: 3607 AN: 152078 Hom.: 143 Cov.: 31 AF XY: 0.0231 AC XY: 1721 AN XY: 74350

African (AFR) AF: 0.0823 AC: 3413 AN: 41472

American (AMR) AF: 0.00903 AC: 138 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.000832 AC: 4 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000397 AC: 27 AN: 67984

Other (OTH) AF: 0.0114 AC: 24 AN: 2110

Alfa AF: 0.00976 Hom.: 172

Bravo AF: 0.0268

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0785 AC: 346

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00762 AC: 925

Asia WGS AF: 0.00722 AC: 26 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	19
DANN	Benign	0.66
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.077
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.79	T
MetaRNN	Benign	0.0025	T
MetaSVM	Uncertain	0.25	D
MutationAssessor	Benign	1.1	L
PhyloP100		1.2
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.46
Sift	Benign	0.90	T
Sift4G	Benign	1.0	T
Vest4		0.23
MVP		0.80
MPC		0.14
ClinPred		0.019	T
GERP RS		4.9
Varity_R		0.11
gMVP		0.31
Mutation Taster		=88/12	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: rs1277017; hg19: chr1-109276068;