rs858312

chr7-23166015-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
KLHL7	NM_001031710.3	c.1177+77C>T		intron_variant		ENST00000339077.10
KLHL7	NM_018846.5	c.1033+77C>T		intron_variant
KLHL7	NR_033328.2	n.1550+77C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLHL7	ENST00000339077.10	c.1177+77C>T		intron_variant		1	NM_001031710.3	P1
KLHL7	ENST00000409689.5	c.1033+77C>T		intron_variant		1
KLHL7	ENST00000521082.5	c.*1185+77C>T		intron_variant, NMD_transcript_variant		1
KLHL7	ENST00000469576.1	n.64+77C>T		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR exome AF: 0.0490

Gnomad4 AMR exome AF: 0.0515

Gnomad4 ASJ exome AF: 0.0598

Gnomad4 EAS exome AF: 0.0195

Gnomad4 SAS exome AF: 0.0832

Gnomad4 FIN exome AF: 0.102

Gnomad4 NFE exome AF: 0.0355

Gnomad4 OTH exome AF: 0.0462

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

Gnomad4 AFR AF: 0.0511

Gnomad4 AMR AF: 0.0538

Gnomad4 ASJ AF: 0.0657

Gnomad4 EAS AF: 0.00965

Gnomad4 SAS AF: 0.0852

Gnomad4 FIN AF: 0.100

Gnomad4 NFE AF: 0.0377

Gnomad4 OTH AF: 0.0455

Alfa AF: 0.0455 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

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

Publications

LitVar

Other links and lift over

dbSNP: rs858312; hg19: chr7-23205634;