chr4-47453118-T-C

Variant names:

• chr4-47453118-T-C
• rs200053687
• NM_017845.5:c.472A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Moderate BP6_Moderate

The NM_017845.5(COMMD8):​c.472A>G​(p.Ile158Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,613,548 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: COMMD8 NM_017845.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.945
• Publications: 3 publications found

Genes affected

COMMD8 (HGNC:26036): (COMM domain containing 8) The protein encoded by this gene binds coiled-coil domain-containing protein 22 (CCDC22), and this complex can regulate the turnover of I-kappa-B and the activation of NF-kappa-B. [provided by RefSeq, Jul 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0758709).
• BP6: Variant 4-47453118-T-C is Benign according to our data. Variant chr4-47453118-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2598739.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017845.5. 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
	COMMD8	NM_017845.5	MANE Select	c.472A>G	p.Ile158Val	missense	Exon 4 of 5	NP_060315.1	Q9NX08
	COMMD8	NM_001329668.2		c.466A>G	p.Ile156Val	missense	Exon 4 of 5	NP_001316597.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COMMD8	ENST00000381571.6	TSL:1 MANE Select	c.472A>G	p.Ile158Val	missense	Exon 4 of 5	ENSP00000370984.4	Q9NX08
	COMMD8	ENST00000952424.1		c.505A>G	p.Ile169Val	missense	Exon 5 of 6	ENSP00000622483.1
	COMMD8	ENST00000860334.1		c.466A>G	p.Ile156Val	missense	Exon 4 of 5	ENSP00000530393.1

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152194 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000107 AC: 27 AN: 251414 AF XY: 0.0000957

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000220

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000116 AC: 170 AN: 1461354 Hom.: 0 Cov.: 30 AF XY: 0.000111 AC XY: 81 AN XY: 727026

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86250

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.000138 AC: 153 AN: 1111536

Other (OTH) AF: 0.000215 AC: 13 AN: 60382

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152194 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74354

African (AFR) AF: 0.00 AC: 0 AN: 41442

American (AMR) AF: 0.0000654 AC: 1 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000160 Hom.: 0

Bravo AF: 0.000102

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000107 AC: 13

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.9
DANN	Benign	0.39
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.3	N
PhyloP100		0.94
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.061
Sift	Benign	0.87	T
Sift4G	Benign	0.74	T
Polyphen		0.0010	B
Vest4		0.13
MVP		0.040
MPC		0.11
ClinPred		0.012	T
GERP RS		3.4
Varity_R		0.016
gMVP		0.12
Mutation Taster		=94/6	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: rs200053687; hg19: chr4-47455135;