7-48046480-C-T

Variant names:

• chr7-48046480-C-T
• rs2708912
• NM_001100159.3:c.371C>T

Variant summary

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

The NM_001100159.3(C7orf57):​c.371C>T​(p.Pro124Leu) variant causes a missense change. The variant allele was found at a frequency of 0.9 in 1,613,174 control chromosomes in the GnomAD database, including 656,402 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 0.86 (56701 hom., cov: 31)
  • Exomes 𝑓: 0.90 (599701 hom.)
• Consequence: C7orf57 NM_001100159.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.91
• Publications: 26 publications found

Genes affected

C7orf57 (HGNC:22247): (chromosome 7 open reading frame 57)

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=2.7126152E-6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100159.3. 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
	C7orf57	NM_001100159.3	MANE Select	c.371C>T	p.Pro124Leu	missense	Exon 5 of 9	NP_001093629.1	Q8NEG2-1
	C7orf57	NM_001267865.2		c.5C>T	p.Pro2Leu	missense	Exon 4 of 8	NP_001254794.1	F5H7J8
	C7orf57	NM_001267866.2		c.5C>T	p.Pro2Leu	missense	Exon 4 of 7	NP_001254795.1	Q8NEG2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C7orf57	ENST00000348904.4	TSL:1 MANE Select	c.371C>T	p.Pro124Leu	missense	Exon 5 of 9	ENSP00000335500.3	Q8NEG2-1
	C7orf57	ENST00000435376.5	TSL:1	c.5C>T	p.Pro2Leu	missense	Exon 4 of 7	ENSP00000391652.1	Q8NEG2-2
	C7orf57	ENST00000430738.5	TSL:5	c.506C>T	p.Pro169Leu	missense	Exon 5 of 9	ENSP00000410944.1	J3KQX6

Frequencies

GnomAD3 genomes AF: 0.859 AC: 130684 AN: 152062 Hom.: 56677 Cov.: 31

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.996

Gnomad AMR AF: 0.870

Gnomad ASJ AF: 0.841

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.813

Gnomad FIN AF: 0.922

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.926

Gnomad OTH AF: 0.873

GnomAD2 exomes AF: 0.872 AC: 216342 AN: 248034 AF XY: 0.874

Gnomad AFR exome AF: 0.744

Gnomad AMR exome AF: 0.852

Gnomad ASJ exome AF: 0.846

Gnomad EAS exome AF: 0.730

Gnomad FIN exome AF: 0.917

Gnomad NFE exome AF: 0.925

Gnomad OTH exome AF: 0.888

GnomAD4 exome AF: 0.904 AC: 1321229 AN: 1460994 Hom.: 599701 Cov.: 50 AF XY: 0.903 AC XY: 656035 AN XY: 726732

African (AFR) AF: 0.745 AC: 24921 AN: 33462

American (AMR) AF: 0.857 AC: 38228 AN: 44598

Ashkenazi Jewish (ASJ) AF: 0.845 AC: 22057 AN: 26110

East Asian (EAS) AF: 0.690 AC: 27343 AN: 39654

South Asian (SAS) AF: 0.819 AC: 70513 AN: 86102

European-Finnish (FIN) AF: 0.919 AC: 49070 AN: 53372

Middle Eastern (MID) AF: 0.903 AC: 5205 AN: 5766

European-Non Finnish (NFE) AF: 0.927 AC: 1030165 AN: 1111580

Other (OTH) AF: 0.890 AC: 53727 AN: 60350

GnomAD4 genome AF: 0.859 AC: 130752 AN: 152180 Hom.: 56701 Cov.: 31 AF XY: 0.858 AC XY: 63803 AN XY: 74390

African (AFR) AF: 0.749 AC: 31045 AN: 41460

American (AMR) AF: 0.870 AC: 13311 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.841 AC: 2920 AN: 3470

East Asian (EAS) AF: 0.729 AC: 3767 AN: 5166

South Asian (SAS) AF: 0.813 AC: 3919 AN: 4822

European-Finnish (FIN) AF: 0.922 AC: 9785 AN: 10610

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.926 AC: 62998 AN: 68024

Other (OTH) AF: 0.868 AC: 1834 AN: 2114

Alfa AF: 0.899 Hom.: 274632

Bravo AF: 0.852

TwinsUK AF: 0.923 AC: 3422

ALSPAC AF: 0.928 AC: 3576

ESP6500AA AF: 0.765 AC: 3169

ESP6500EA AF: 0.929 AC: 7793

ExAC AF: 0.870 AC: 105232

Asia WGS AF: 0.766 AC: 2663 AN: 3478

EpiCase AF: 0.924

EpiControl AF: 0.924

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.75	T
MetaRNN	Benign	0.0000027	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		4.9
PROVEAN	Pathogenic	-8.4	D
REVEL	Benign	0.18
Sift	Benign	0.075	T
Sift4G	Uncertain	0.042	D
Polyphen		0.86	P
Vest4		0.54
MPC		0.21
ClinPred		0.067	T
GERP RS		5.3
Varity_R		0.44
gMVP		0.54
Mutation Taster		=90/10	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2708912; hg19: chr7-48086077; COSMIC: COSV62361797; COSMIC: COSV62361797;