rs858312

Variant names:

• chr7-23166015-C-T
• rs858312
• NM_001031710.3:c.1177+77C>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.1177+77C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0431 in 1,467,370 control chromosomes in the GnomAD database, including 1,664 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 0.048 (212 hom., cov: 32)
  • Exomes 𝑓: 0.042 (1452 hom.)
• Consequence: KLHL7 NM_001031710.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.371
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL7	NM_001031710.3	c.1177+77C>T		intron_variant	Intron 8 of 10	ENST00000339077.10	NP_001026880.2
KLHL7	NM_018846.5	c.1033+77C>T		intron_variant	Intron 8 of 10		NP_061334.4
KLHL7	NR_033328.2	n.1550+77C>T		intron_variant	Intron 9 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL7	ENST00000339077.10	c.1177+77C>T		intron_variant	Intron 8 of 10	1	NM_001031710.3	ENSP00000343273.4
KLHL7	ENST00000409689.5	c.1033+77C>T		intron_variant	Intron 8 of 10	1		ENSP00000386263.1
KLHL7	ENST00000521082.5	n.*1185+77C>T		intron_variant	Intron 9 of 11	1		ENSP00000430351.1
KLHL7	ENST00000469576.1	n.64+77C>T		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.0483 AC: 7350 AN: 152048 Hom.: 210 Cov.: 32

Gnomad AFR AF: 0.0508

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0535

Gnomad ASJ AF: 0.0657

Gnomad EAS AF: 0.00982

Gnomad SAS AF: 0.0853

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0377

Gnomad OTH AF: 0.0464

GnomAD4 exome AF: 0.0425 AC: 55870 AN: 1315204 Hom.: 1452 AF XY: 0.0436 AC XY: 28849 AN XY: 662330

African (AFR) AF: 0.0490 AC: 1484 AN: 30316

American (AMR) AF: 0.0515 AC: 2265 AN: 44016

Ashkenazi Jewish (ASJ) AF: 0.0598 AC: 1502 AN: 25110

East Asian (EAS) AF: 0.0195 AC: 761 AN: 39028

South Asian (SAS) AF: 0.0832 AC: 6852 AN: 82384

European-Finnish (FIN) AF: 0.102 AC: 5416 AN: 53050

Middle Eastern (MID) AF: 0.0439 AC: 177 AN: 4032

European-Non Finnish (NFE) AF: 0.0355 AC: 34857 AN: 981898

Other (OTH) AF: 0.0462 AC: 2556 AN: 55370

GnomAD4 genome AF: 0.0484 AC: 7368 AN: 152166 Hom.: 212 Cov.: 32 AF XY: 0.0516 AC XY: 3834 AN XY: 74372

African (AFR) AF: 0.0511 AC: 2122 AN: 41526

American (AMR) AF: 0.0538 AC: 823 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0657 AC: 228 AN: 3468

East Asian (EAS) AF: 0.00965 AC: 50 AN: 5182

South Asian (SAS) AF: 0.0852 AC: 410 AN: 4814

European-Finnish (FIN) AF: 0.100 AC: 1062 AN: 10570

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0377 AC: 2564 AN: 67988

Other (OTH) AF: 0.0455 AC: 96 AN: 2112

Alfa AF: 0.0456 Hom.: 32

Bravo AF: 0.0434

Asia WGS AF: 0.0640 AC: 222 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.9
DANN	Benign	0.63
PhyloP100		0.37
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: rs858312; hg19: chr7-23205634;