7-23125082-C-T

Variant names:

• chr7-23125082-C-T
• rs15775
• NM_001031710.3:c.352C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001031710.3(KLHL7):​c.352C>T​(p.Leu118Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 1,610,180 control chromosomes in the GnomAD database, including 115,329 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (15691 hom., cov: 32)
  • Exomes 𝑓: 0.36 (99638 hom.)
• Consequence: KLHL7 NM_001031710.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.43
• Publications: 28 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, Ambry Genetics, Illumina
• 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 7-23125082-C-T is Benign according to our data. Variant chr7-23125082-C-T is described in ClinVar as Benign. ClinVar VariationId is 359798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.43 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.636 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL7	NM_001031710.3	MANE Select	c.352C>T	p.Leu118Leu	synonymous	Exon 4 of 11	NP_001026880.2
	KLHL7	NM_018846.5		c.208C>T	p.Leu70Leu	synonymous	Exon 4 of 11	NP_061334.4
	KLHL7	NM_001172428.2		c.352C>T	p.Leu118Leu	synonymous	Exon 4 of 5	NP_001165899.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL7	ENST00000339077.10	TSL:1 MANE Select	c.352C>T	p.Leu118Leu	synonymous	Exon 4 of 11	ENSP00000343273.4
	KLHL7	ENST00000409689.5	TSL:1	c.208C>T	p.Leu70Leu	synonymous	Exon 4 of 11	ENSP00000386263.1
	KLHL7	ENST00000322275.9	TSL:1	c.352C>T	p.Leu118Leu	synonymous	Exon 4 of 5	ENSP00000323270.5

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65747 AN: 151950 Hom.: 15658 Cov.: 32

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.440

GnomAD2 exomes AF: 0.345 AC: 86522 AN: 251008 AF XY: 0.341

Gnomad AFR exome AF: 0.651

Gnomad AMR exome AF: 0.221

Gnomad ASJ exome AF: 0.372

Gnomad EAS exome AF: 0.323

Gnomad FIN exome AF: 0.280

Gnomad NFE exome AF: 0.373

Gnomad OTH exome AF: 0.352

GnomAD4 exome AF: 0.363 AC: 530014 AN: 1458112 Hom.: 99638 Cov.: 31 AF XY: 0.360 AC XY: 261264 AN XY: 725482

African (AFR) AF: 0.654 AC: 21843 AN: 33404

American (AMR) AF: 0.233 AC: 10414 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 9766 AN: 26106

East Asian (EAS) AF: 0.343 AC: 13564 AN: 39600

South Asian (SAS) AF: 0.263 AC: 22644 AN: 86162

European-Finnish (FIN) AF: 0.288 AC: 15376 AN: 53372

Middle Eastern (MID) AF: 0.395 AC: 2276 AN: 5756

European-Non Finnish (NFE) AF: 0.371 AC: 411268 AN: 1108748

Other (OTH) AF: 0.379 AC: 22863 AN: 60256

GnomAD4 genome AF: 0.433 AC: 65824 AN: 152068 Hom.: 15691 Cov.: 32 AF XY: 0.424 AC XY: 31495 AN XY: 74318

African (AFR) AF: 0.642 AC: 26632 AN: 41462

American (AMR) AF: 0.341 AC: 5205 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1348 AN: 3470

East Asian (EAS) AF: 0.326 AC: 1687 AN: 5180

South Asian (SAS) AF: 0.265 AC: 1277 AN: 4822

European-Finnish (FIN) AF: 0.275 AC: 2902 AN: 10568

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25438 AN: 67974

Other (OTH) AF: 0.443 AC: 935 AN: 2110

Alfa AF: 0.396 Hom.: 42618

Bravo AF: 0.445

Asia WGS AF: 0.362 AC: 1256 AN: 3472

EpiCase AF: 0.382

EpiControl AF: 0.381

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	PERCHING syndrome (1)
-	-	1	Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	8.2
DANN	Benign	0.80
PhyloP100		1.4
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: rs15775; hg19: chr7-23164701;