rs1046655

Variant names:

• chr4-39126127-G-A
• rs1046655
• NM_015990.5:c.*5061G>A

Variant summary

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

The NM_015990.5(KLHL5):​c.*5061G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 151,984 control chromosomes in the GnomAD database, including 21,556 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 0.53 (21556 hom., cov: 32)
• Consequence: KLHL5 NM_015990.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.499
• Publications: 9 publications found

Genes affected

KLHL5 (HGNC:6356): (kelch like family member 5) Predicted to enable actin binding activity. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000249207 (HGNC:58761):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015990.5. 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
	KLHL5	NM_015990.5	MANE Select	c.*5061G>A		3_prime_UTR	Exon 11 of 11	NP_057074.4
	KLHL5	NM_001007075.2		c.*5061G>A		3_prime_UTR	Exon 12 of 12	NP_001007076.1	Q7Z6D5
	KLHL5	NM_199039.4		c.*5061G>A		3_prime_UTR	Exon 10 of 10	NP_950240.3	A0A804C9D6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL5	ENST00000504108.7	TSL:2 MANE Select	c.*5061G>A		3_prime_UTR	Exon 11 of 11	ENSP00000423897.2	Q96PQ7-6
	KLHL5	ENST00000515612.1	TSL:5	c.745-567G>A		intron	N/A	ENSP00000425512.1	H0Y9Y5
	ENSG00000249207	ENST00000509449.1	TSL:3	n.111+581C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79781 AN: 151866 Hom.: 21546 Cov.: 32

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.580

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.525 AC: 79826 AN: 151984 Hom.: 21556 Cov.: 32 AF XY: 0.526 AC XY: 39062 AN XY: 74294

African (AFR) AF: 0.383 AC: 15891 AN: 41458

American (AMR) AF: 0.589 AC: 8994 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1705 AN: 3458

East Asian (EAS) AF: 0.491 AC: 2533 AN: 5160

South Asian (SAS) AF: 0.519 AC: 2499 AN: 4814

European-Finnish (FIN) AF: 0.575 AC: 6066 AN: 10552

Middle Eastern (MID) AF: 0.575 AC: 168 AN: 292

European-Non Finnish (NFE) AF: 0.595 AC: 40420 AN: 67954

Other (OTH) AF: 0.542 AC: 1144 AN: 2112

Alfa AF: 0.468 Hom.: 2067

Bravo AF: 0.519

Asia WGS AF: 0.513 AC: 1785 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.96
DANN	Benign	0.80
PhyloP100		-0.50
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1046655; hg19: chr4-39127747;