chr7-23114256-C-T

Variant names:

• chr7-23114256-C-T
• rs764533
• NM_001031710.3:c.120+8110C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001031710.3(KLHL7):​c.120+8110C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 150,380 control chromosomes in the GnomAD database, including 18,346 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.

• Frequency: Genomes: 𝑓 0.46 (18346 hom., cov: 32)
• Consequence: KLHL7 NM_001031710.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.361
• Publications: 12 publications found

Genes affected

KLHL7 (HGNC:15646): (kelch like family member 7) This gene encodes a BTB-Kelch-related protein. The encoded protein may be involved in protein degradation. Mutations in this gene have been associated with retinitis pigmentosa 42. [provided by RefSeq, Feb 2010]

KLHL7 Gene-Disease associations (from GenCC):

• PERCHING syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Illumina, Ambry Genetics
• retinitis pigmentosa 42

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• cold-induced sweating syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031710.3. 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
	KLHL7	NM_001031710.3	MANE Select	c.120+8110C>T		intron	N/A	NP_001026880.2	Q8IXQ5-1
	KLHL7	NM_018846.5		c.-25+7462C>T		intron	N/A	NP_061334.4
	KLHL7	NM_001172428.2		c.120+8110C>T		intron	N/A	NP_001165899.1	Q8IXQ5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL7	ENST00000339077.10	TSL:1 MANE Select	c.120+8110C>T		intron	N/A	ENSP00000343273.4	Q8IXQ5-1
	KLHL7	ENST00000409689.5	TSL:1	c.-25+7462C>T		intron	N/A	ENSP00000386263.1	Q8IXQ5-5
	KLHL7	ENST00000322275.9	TSL:1	c.120+8110C>T		intron	N/A	ENSP00000323270.5	Q8IXQ5-3

Frequencies

GnomAD3 genomes AF: 0.464 AC: 69653 AN: 150270 Hom.: 18306 Cov.: 32

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.464

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.464 AC: 69736 AN: 150380 Hom.: 18346 Cov.: 32 AF XY: 0.453 AC XY: 33356 AN XY: 73578

African (AFR) AF: 0.759 AC: 30338 AN: 39984

American (AMR) AF: 0.352 AC: 5345 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1346 AN: 3470

East Asian (EAS) AF: 0.326 AC: 1685 AN: 5168

South Asian (SAS) AF: 0.266 AC: 1275 AN: 4800

European-Finnish (FIN) AF: 0.275 AC: 2901 AN: 10554

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.375 AC: 25469 AN: 67952

Other (OTH) AF: 0.468 AC: 975 AN: 2084

Alfa AF: 0.361 Hom.: 5153

Bravo AF: 0.475

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.2
DANN	Benign	0.66
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism (auto)

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: rs764533; hg19: chr7-23153875;