chr6-31112546-G-T

Variant names:

• chr6-31112546-G-T
• rs2233971
• NM_014070.3:c.10C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_014070.3(C6orf15):​c.10C>A​(p.Arg4Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 1,545,430 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0064 (13 hom., cov: 33)
  • Exomes 𝑓: 0.00073 (8 hom.)
• Consequence: C6orf15 NM_014070.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 5 publications found

Genes affected

C6orf15 (HGNC:13927): (chromosome 6 open reading frame 15) Predicted to enable several functions, including collagen V binding activity; fibronectin binding activity; and glycosaminoglycan binding activity. Predicted to be involved in extracellular matrix organization. Predicted to be located in interstitial matrix. Predicted to be active in extracellular matrix. [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=0.0026617348).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00638 (972/152356) while in subpopulation AFR AF = 0.0219 (910/41584). AF 95% confidence interval is 0.0207. There are 13 homozygotes in GnomAd4. There are 459 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014070.3. 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
	C6orf15	NM_014070.3	MANE Select	c.10C>A	p.Arg4Ser	missense	Exon 1 of 2	NP_054789.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C6orf15	ENST00000259870.4	TSL:1 MANE Select	c.10C>A	p.Arg4Ser	missense	Exon 1 of 2	ENSP00000259870.3

Frequencies

GnomAD3 genomes AF: 0.00636 AC: 968 AN: 152238 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.0219

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00159 AC: 240 AN: 150860 AF XY: 0.00104

Gnomad AFR exome AF: 0.0219

Gnomad AMR exome AF: 0.00140

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000172

Gnomad OTH exome AF: 0.000472

GnomAD4 exome AF: 0.000732 AC: 1020 AN: 1393074 Hom.: 8 Cov.: 31 AF XY: 0.000654 AC XY: 449 AN XY: 686920

African (AFR) AF: 0.0241 AC: 754 AN: 31346

American (AMR) AF: 0.00150 AC: 52 AN: 34554

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24742

East Asian (EAS) AF: 0.00 AC: 0 AN: 35658

South Asian (SAS) AF: 0.000204 AC: 16 AN: 78542

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49190

Middle Eastern (MID) AF: 0.00141 AC: 8 AN: 5658

European-Non Finnish (NFE) AF: 0.0000846 AC: 91 AN: 1075670

Other (OTH) AF: 0.00172 AC: 99 AN: 57714

GnomAD4 genome AF: 0.00638 AC: 972 AN: 152356 Hom.: 13 Cov.: 33 AF XY: 0.00616 AC XY: 459 AN XY: 74510

African (AFR) AF: 0.0219 AC: 910 AN: 41584

American (AMR) AF: 0.00288 AC: 44 AN: 15302

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68036

Other (OTH) AF: 0.00425 AC: 9 AN: 2116

Alfa AF: 0.00169 Hom.: 1

Bravo AF: 0.00778

ESP6500AA AF: 0.0233 AC: 100

ESP6500EA AF: 0.000359 AC: 3

ExAC AF: 0.00137 AC: 136

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.51
DANN	Benign	0.96
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.039	N
MetaRNN	Benign	0.0027	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.5	L
PhyloP100		-1.4
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.053
Sift	Benign	0.41	T
Sift4G	Benign	0.40	T
Polyphen		0.80	P
Vest4		0.13
MVP		0.19
MPC		0.85
ClinPred		0.051	T
GERP RS		-2.4
PromoterAI		0.055	Neutral
Varity_R		0.063
gMVP		0.16
Mutation Taster		=95/5	polymorphism

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: rs2233971; hg19: chr6-31080323;