rs2242655

Positions:

• chr6-31659672-C-G

Variant summary

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

The NM_021184.4(C6orf47):​c.276G>C​(p.Lys92Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 1,612,968 control chromosomes in the GnomAD database, including 17,000 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.14 (1740 hom., cov: 32)
  • Exomes 𝑓: 0.14 (15260 hom.)
• Consequence: C6orf47 NM_021184.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.451

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=0.0035974681).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C6orf47	NM_021184.4	c.276G>C	p.Lys92Asn	missense_variant	1/1	ENST00000375911.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C6orf47	ENST00000375911.2	c.276G>C	p.Lys92Asn	missense_variant	1/1		NM_021184.4	P1
C6orf47-AS1	ENST00000422049.1	n.352-728C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20589 AN: 152122 Hom.: 1736 Cov.: 32

Gnomad AFR AF: 0.0807

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.0300

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.107

GnomAD3 exomes AF: 0.152 AC: 37393 AN: 246464 Hom.: 3582 AF XY: 0.145 AC XY: 19441 AN XY: 134370

Gnomad AFR exome AF: 0.0811

Gnomad AMR exome AF: 0.234

Gnomad ASJ exome AF: 0.0290

Gnomad EAS exome AF: 0.141

Gnomad SAS exome AF: 0.101

Gnomad FIN exome AF: 0.313

Gnomad NFE exome AF: 0.132

Gnomad OTH exome AF: 0.138

GnomAD4 exome AF: 0.135 AC: 197583 AN: 1460728 Hom.: 15260 Cov.: 33 AF XY: 0.133 AC XY: 96501 AN XY: 726678

Gnomad4 AFR exome AF: 0.0693

Gnomad4 AMR exome AF: 0.224

Gnomad4 ASJ exome AF: 0.0308

Gnomad4 EAS exome AF: 0.215

Gnomad4 SAS exome AF: 0.101

Gnomad4 FIN exome AF: 0.310

Gnomad4 NFE exome AF: 0.129

Gnomad4 OTH exome AF: 0.122

GnomAD4 genome AF: 0.135 AC: 20612 AN: 152240 Hom.: 1740 Cov.: 32 AF XY: 0.144 AC XY: 10698 AN XY: 74424

Gnomad4 AFR AF: 0.0806

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.0300

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.106

Alfa AF: 0.121 Hom.: 950

Bravo AF: 0.125

TwinsUK AF: 0.129 AC: 479

ALSPAC AF: 0.124 AC: 478

ESP6500AA AF: 0.0851 AC: 257

ESP6500EA AF: 0.134 AC: 724

ExAC AF: 0.146 AC: 17102

Asia WGS AF: 0.141 AC: 491 AN: 3478

EpiCase AF: 0.113

EpiControl AF: 0.115

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.020	T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.37	T
MetaRNN	Benign	0.0036	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L
MutationTaster	Benign	0.96	P
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.060
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.018	D
Polyphen		0.98	D
Vest4		0.030
MutPred		0.14		Loss of ubiquitination at K92 (P = 0.0047);
MPC		0.78
ClinPred		0.015	T
GERP RS		3.5
Varity_R		0.095
gMVP		0.035

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: rs2242655; hg19: chr6-31627449; COSMIC: COSV63263650; COSMIC: COSV63263650;