chr7-23105882-C-T

Variant names:

• chr7-23105882-C-T
• rs545540476
• NM_001031710.3:c.-145C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS1_Supporting

The NM_001031710.3(KLHL7):​c.-145C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000922 in 1,304,162 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00096 (1 hom.)
• Consequence: KLHL7 NM_001031710.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.67
• Publications: 0 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-DT (HGNC:43431): (KLHL7 divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000656 (100/152340) while in subpopulation NFE AF = 0.00118 (80/68028). AF 95% confidence interval is 0.000968. There are 0 homozygotes in GnomAd4. There are 41 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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.-145C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	NP_001026880.2	Q8IXQ5-1
	KLHL7	NM_001031710.3	MANE Select	c.-145C>T		5_prime_UTR	Exon 1 of 11	NP_001026880.2	Q8IXQ5-1
	KLHL7	NM_001172428.2		c.-145C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	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.-145C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	ENSP00000343273.4	Q8IXQ5-1
	KLHL7	ENST00000322275.9	TSL:1	c.-145C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000323270.5	Q8IXQ5-3
	KLHL7	ENST00000339077.10	TSL:1 MANE Select	c.-145C>T		5_prime_UTR	Exon 1 of 11	ENSP00000343273.4	Q8IXQ5-1

Frequencies

GnomAD3 genomes AF: 0.000657 AC: 100 AN: 152222 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00118

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000522 AC: 71 AN: 136114 AF XY: 0.000501

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000207

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.00109

Gnomad OTH exome AF: 0.00122

GnomAD4 exome AF: 0.000958 AC: 1103 AN: 1151822 Hom.: 1 Cov.: 16 AF XY: 0.000911 AC XY: 526 AN XY: 577598

African (AFR) AF: 0.000185 AC: 5 AN: 27082

American (AMR) AF: 0.000202 AC: 7 AN: 34732

Ashkenazi Jewish (ASJ) AF: 0.0000427 AC: 1 AN: 23404

East Asian (EAS) AF: 0.00 AC: 0 AN: 34366

South Asian (SAS) AF: 0.0000136 AC: 1 AN: 73788

European-Finnish (FIN) AF: 0.000306 AC: 10 AN: 32646

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3602

European-Non Finnish (NFE) AF: 0.00119 AC: 1037 AN: 872438

Other (OTH) AF: 0.000844 AC: 42 AN: 49764

GnomAD4 genome AF: 0.000656 AC: 100 AN: 152340 Hom.: 0 Cov.: 33 AF XY: 0.000550 AC XY: 41 AN XY: 74494

African (AFR) AF: 0.000337 AC: 14 AN: 41578

American (AMR) AF: 0.000196 AC: 3 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00118 AC: 80 AN: 68028

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000556 Hom.: 0

Bravo AF: 0.000604

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.9
DANN	Benign	0.84
PhyloP100		-1.7
PromoterAI		0.021	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Mutation Taster		=287/13	polymorphism

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: rs545540476; hg19: chr7-23145501;