rs9394939

Variant names:

• chr6-43046560-T-C
• rs9394939
• NM_014780.5:c.2439A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-43046560-T-C
• chr6-43046560-T-A
• chr6-43046560-T-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014780.5(CUL7):​c.2439A>G​(p.Gln813Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.972 in 1,614,046 control chromosomes in the GnomAD database, including 762,366 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.98 (73000 hom., cov: 31)
  • Exomes 𝑓: 0.97 (689366 hom.)
• Consequence: CUL7 NM_014780.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.505
• Publications: 16 publications found

Genes affected

CUL7 (HGNC:21024): (cullin 7) The protein encoded by this gene is a component of an E3 ubiquitin-protein ligase complex. The encoded protein interacts with TP53, CUL9, and FBXW8 proteins. Defects in this gene are a cause of 3M syndrome type 1 (3M1). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2009]

KLC4 (HGNC:21624): (kinesin light chain 4) Predicted to be located in cytoplasm and microtubule. Predicted to be part of kinesin complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 6-43046560-T-C is Benign according to our data. Variant chr6-43046560-T-C is described in ClinVar as Benign. ClinVar VariationId is 260437.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.505 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.986 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014780.5. 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
	CUL7	NM_014780.5	MANE Select	c.2439A>G	p.Gln813Gln	synonymous	Exon 11 of 26	NP_055595.2
	CUL7	NM_001168370.2		c.2535A>G	p.Gln845Gln	synonymous	Exon 11 of 26	NP_001161842.2	A0A669KBH4
	CUL7	NM_001374872.1		c.2535A>G	p.Gln845Gln	synonymous	Exon 11 of 26	NP_001361801.1	A0A669KBH4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUL7	ENST00000265348.9	TSL:1 MANE Select	c.2439A>G	p.Gln813Gln	synonymous	Exon 11 of 26	ENSP00000265348.4	Q14999-1
	CUL7	ENST00000674100.1		c.2535A>G	p.Gln845Gln	synonymous	Exon 11 of 26	ENSP00000501292.1	A0A669KBH4
	CUL7	ENST00000674134.1		c.2535A>G	p.Gln845Gln	synonymous	Exon 11 of 26	ENSP00000501068.1	A0A669KBH4

Frequencies

GnomAD3 genomes AF: 0.979 AC: 148920 AN: 152106 Hom.: 72938 Cov.: 31

Gnomad AFR AF: 0.994

Gnomad AMI AF: 0.993

Gnomad AMR AF: 0.982

Gnomad ASJ AF: 0.895

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.988

Gnomad FIN AF: 0.995

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.969

Gnomad OTH AF: 0.973

GnomAD2 exomes AF: 0.976 AC: 245352 AN: 251320 AF XY: 0.975

Gnomad AFR exome AF: 0.995

Gnomad AMR exome AF: 0.985

Gnomad ASJ exome AF: 0.894

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.992

Gnomad NFE exome AF: 0.968

Gnomad OTH exome AF: 0.971

GnomAD4 exome AF: 0.971 AC: 1419492 AN: 1461822 Hom.: 689366 Cov.: 119 AF XY: 0.971 AC XY: 706150 AN XY: 727196

African (AFR) AF: 0.995 AC: 33321 AN: 33480

American (AMR) AF: 0.983 AC: 43961 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.891 AC: 23285 AN: 26134

East Asian (EAS) AF: 0.999 AC: 39675 AN: 39700

South Asian (SAS) AF: 0.989 AC: 85349 AN: 86258

European-Finnish (FIN) AF: 0.992 AC: 52966 AN: 53420

Middle Eastern (MID) AF: 0.933 AC: 5384 AN: 5768

European-Non Finnish (NFE) AF: 0.969 AC: 1076975 AN: 1111954

Other (OTH) AF: 0.970 AC: 58576 AN: 60396

GnomAD4 genome AF: 0.979 AC: 149041 AN: 152224 Hom.: 73000 Cov.: 31 AF XY: 0.981 AC XY: 73031 AN XY: 74438

African (AFR) AF: 0.994 AC: 41259 AN: 41514

American (AMR) AF: 0.982 AC: 15008 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.895 AC: 3106 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5172 AN: 5174

South Asian (SAS) AF: 0.988 AC: 4775 AN: 4832

European-Finnish (FIN) AF: 0.995 AC: 10576 AN: 10626

Middle Eastern (MID) AF: 0.949 AC: 277 AN: 292

European-Non Finnish (NFE) AF: 0.969 AC: 65910 AN: 68006

Other (OTH) AF: 0.973 AC: 2052 AN: 2108

Alfa AF: 0.970 Hom.: 59471

Bravo AF: 0.978

Asia WGS AF: 0.992 AC: 3449 AN: 3478

EpiCase AF: 0.969

EpiControl AF: 0.964

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	3M syndrome 1 (2)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	5.7
DANN	Benign	0.72
PhyloP100		0.51
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs9394939; hg19: chr6-43014298; COSMIC: COSV99538180;