rs3130617

chr6-31659746-C-T

Variant summary

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

The NM_021184.4(C6orf47):c.202G>A(p.Gly68Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 1,612,754 control chromosomes in the GnomAD database, including 456,605 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.75 (42636 hom., cov: 32)
  • Exomes 𝑓: 0.75 (413969 hom.)
• Consequence: C6orf47 NM_021184.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.360

Genes affected

C6orf47 (HGNC:19076): (chromosome 6 open reading frame 47)

C6orf47-AS1 (HGNC:39767): (C6orf47 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1138699E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C6orf47	NM_021184.4	c.202G>A	p.Gly68Arg	missense_variant	1/1	ENST00000375911.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C6orf47	ENST00000375911.2	c.202G>A	p.Gly68Arg	missense_variant	1/1		NM_021184.4	P1
C6orf47-AS1	ENST00000422049.1	n.352-654C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.746 AC: 113310 AN: 151956 Hom.: 42607 Cov.: 32

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.847

Gnomad AMR AF: 0.771

Gnomad ASJ AF: 0.884

Gnomad EAS AF: 0.973

Gnomad SAS AF: 0.840

Gnomad FIN AF: 0.815

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.762

GnomAD3 exomes AF: 0.794 AC: 195632 AN: 246376 Hom.: 78506 AF XY: 0.793 AC XY: 106440 AN XY: 134304

Gnomad AFR exome AF: 0.674

Gnomad AMR exome AF: 0.851

Gnomad ASJ exome AF: 0.894

Gnomad EAS exome AF: 0.980

Gnomad SAS exome AF: 0.810

Gnomad FIN exome AF: 0.802

Gnomad NFE exome AF: 0.748

Gnomad OTH exome AF: 0.782

GnomAD4 exome AF: 0.750 AC: 1095381 AN: 1460680 Hom.: 413969 Cov.: 86 AF XY: 0.752 AC XY: 546719 AN XY: 726644

Gnomad4 AFR exome AF: 0.672

Gnomad4 AMR exome AF: 0.843

Gnomad4 ASJ exome AF: 0.890

Gnomad4 EAS exome AF: 0.982

Gnomad4 SAS exome AF: 0.810

Gnomad4 FIN exome AF: 0.795

Gnomad4 NFE exome AF: 0.729

Gnomad4 OTH exome AF: 0.762

GnomAD4 genome AF: 0.746 AC: 113386 AN: 152074 Hom.: 42636 Cov.: 32 AF XY: 0.752 AC XY: 55935 AN XY: 74354

Gnomad4 AFR AF: 0.672

Gnomad4 AMR AF: 0.772

Gnomad4 ASJ AF: 0.884

Gnomad4 EAS AF: 0.973

Gnomad4 SAS AF: 0.839

Gnomad4 FIN AF: 0.815

Gnomad4 NFE AF: 0.740

Gnomad4 OTH AF: 0.766

Alfa AF: 0.759 Hom.: 78828

Bravo AF: 0.740

TwinsUK AF: 0.730 AC: 2705

ALSPAC AF: 0.720 AC: 2775

ESP6500AA AF: 0.689 AC: 2081

ESP6500EA AF: 0.743 AC: 4028

ExAC AF: 0.788 AC: 92193

Asia WGS AF: 0.905 AC: 3146 AN: 3478

EpiCase AF: 0.767

EpiControl AF: 0.770

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.80
Cadd	Benign	2.5
Dann	Benign	0.53
DEOGEN2	Benign	0.0022	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.27	T
MetaRNN	Benign	0.0000011	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.26	N
MutationTaster	Benign	1.0	P
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.028
Sift	Benign	0.87	T
Sift4G	Benign	0.14	T
Polyphen		0.0	B
Vest4		0.0080
MutPred		0.11		Gain of MoRF binding (P = 0.0084);
MPC		0.34
ClinPred		0.011	T
GERP RS		-0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.058
gMVP		0.0079

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: rs3130617; hg19: chr6-31627523;