rs35820949

Variant names:

• chr15-89630503-C-CAG
• rs35820949
• NM_198525.3:c.3112-11_3112-10insCT

Your query was ambiguous. Multiple possible variants found:

• chr15-89630503-C-CAG
• chr15-89630503-C-CA
• chr15-89630503-C-CAA
• chr15-89630503-C-CAGACAG
• chr15-89630503-C-CAGG
• chr15-89630503-C-CCG

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_198525.3(KIF7):​c.3112-11_3112-10insCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 1,548,200 control chromosomes in the GnomAD database, including 253,302 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.56 (24302 hom., cov: 0)
  • Exomes 𝑓: 0.57 (229000 hom.)
• Consequence: KIF7 NM_198525.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.261
• Publications: 7 publications found

Genes affected

KIF7 (HGNC:30497): (kinesin family member 7) This gene encodes a cilia-associated protein belonging to the kinesin family. This protein plays a role in the sonic hedgehog (SHH) signaling pathway through the regulation of GLI transcription factors. It functions as a negative regulator of the SHH pathway by preventing inappropriate activation of GLI2 in the absence of ligand, and as a positive regulator by preventing the processing of GLI3 into its repressor form. Mutations in this gene have been associated with various ciliopathies. [provided by RefSeq, Oct 2011]

TICRR (HGNC:28704): (TOPBP1 interacting checkpoint and replication regulator) Enables chromatin binding activity. Involved in regulation of DNA-dependent DNA replication initiation. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 15-89630503-C-CAG is Benign according to our data. Variant chr15-89630503-C-CAG is described in ClinVar as Benign. ClinVar VariationId is 263145.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198525.3. 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
	KIF7	NM_198525.3	MANE Select	c.3112-11_3112-10insCT		intron	N/A	NP_940927.2	Q2M1P5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF7	ENST00000394412.8	TSL:5 MANE Select	c.3112-11_3112-10insCT		intron	N/A	ENSP00000377934.3	Q2M1P5
	TICRR	ENST00000561095.1	TSL:1	n.*1170_*1171insAG		non_coding_transcript_exon	Exon 4 of 4	ENSP00000453922.1	H0YN97
	TICRR	ENST00000561095.1	TSL:1	n.*1170_*1171insAG		3_prime_UTR	Exon 4 of 4	ENSP00000453922.1	H0YN97

Frequencies

GnomAD3 genomes AF: 0.563 AC: 85506 AN: 151820 Hom.: 24273 Cov.: 0

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.548

GnomAD2 exomes AF: 0.527 AC: 81910 AN: 155468 AF XY: 0.528

Gnomad AFR exome AF: 0.592

Gnomad AMR exome AF: 0.432

Gnomad ASJ exome AF: 0.533

Gnomad EAS exome AF: 0.326

Gnomad FIN exome AF: 0.611

Gnomad NFE exome AF: 0.585

Gnomad OTH exome AF: 0.528

GnomAD4 exome AF: 0.570 AC: 795399 AN: 1396262 Hom.: 229000 Cov.: 30 AF XY: 0.568 AC XY: 391080 AN XY: 688922

African (AFR) AF: 0.587 AC: 18544 AN: 31598

American (AMR) AF: 0.438 AC: 15634 AN: 35716

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 13540 AN: 25174

East Asian (EAS) AF: 0.308 AC: 11035 AN: 35790

South Asian (SAS) AF: 0.504 AC: 39917 AN: 79258

European-Finnish (FIN) AF: 0.610 AC: 29209 AN: 47854

Middle Eastern (MID) AF: 0.474 AC: 2358 AN: 4976

European-Non Finnish (NFE) AF: 0.588 AC: 633368 AN: 1078000

Other (OTH) AF: 0.549 AC: 31794 AN: 57896

GnomAD4 genome AF: 0.563 AC: 85580 AN: 151938 Hom.: 24302 Cov.: 0 AF XY: 0.559 AC XY: 41544 AN XY: 74256

African (AFR) AF: 0.587 AC: 24316 AN: 41436

American (AMR) AF: 0.478 AC: 7299 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1845 AN: 3460

East Asian (EAS) AF: 0.337 AC: 1742 AN: 5162

South Asian (SAS) AF: 0.480 AC: 2314 AN: 4820

European-Finnish (FIN) AF: 0.612 AC: 6443 AN: 10530

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.585 AC: 39748 AN: 67940

Other (OTH) AF: 0.547 AC: 1155 AN: 2112

Alfa AF: 0.500 Hom.: 2439

Bravo AF: 0.553

Asia WGS AF: 0.424 AC: 1476 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	Acrocallosal syndrome (3)
-	-	1	Hydrolethalus syndrome 2 (1)
-	-	1	Multiple epiphyseal dysplasia, Al-Gazali type (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.26
Mutation Taster		=23/77	disease causing

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs35820949; hg19: chr15-90173734; COSMIC: COSV108039185;