19-18671567-A-G

Variant names:

• chr19-18671567-A-G
• rs876982
• NM_018316.3:c.*2322A>G

Variant summary

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

The NM_018316.3(KLHL26):​c.*2322A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 152,190 control chromosomes in the GnomAD database, including 38,503 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 0.70 (38497 hom., cov: 33)
  • Exomes 𝑓: 0.56 (6 hom.)
• Consequence: KLHL26 NM_018316.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.587
• Publications: 12 publications found

Genes affected

KLHL26 (HGNC:25623): (kelch like family member 26)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL26	NM_018316.3	c.*2322A>G		3_prime_UTR_variant	Exon 3 of 3	ENST00000300976.9	NP_060786.1
KLHL26	NM_001345982.2	c.*2322A>G		3_prime_UTR_variant	Exon 4 of 4		NP_001332911.1
KLHL26	NM_001345983.2	c.*2322A>G		3_prime_UTR_variant	Exon 3 of 3		NP_001332912.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL26	ENST00000300976.9	c.*2322A>G		3_prime_UTR_variant	Exon 3 of 3	1	NM_018316.3	ENSP00000300976.3

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106727 AN: 152036 Hom.: 38444 Cov.: 33

Gnomad AFR AF: 0.882

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.655

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.622

Gnomad OTH AF: 0.661

GnomAD4 exome AF: 0.556 AC: 20 AN: 36 Hom.: 6 Cov.: 0 AF XY: 0.607 AC XY: 17 AN XY: 28

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 3 AN: 6

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.545 AC: 12 AN: 22

Other (OTH) AF: 0.500 AC: 3 AN: 6

GnomAD4 genome AF: 0.702 AC: 106842 AN: 152154 Hom.: 38497 Cov.: 33 AF XY: 0.702 AC XY: 52230 AN XY: 74406

African (AFR) AF: 0.882 AC: 36633 AN: 41544

American (AMR) AF: 0.660 AC: 10093 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1847 AN: 3466

East Asian (EAS) AF: 0.655 AC: 3382 AN: 5160

South Asian (SAS) AF: 0.614 AC: 2960 AN: 4824

European-Finnish (FIN) AF: 0.711 AC: 7532 AN: 10594

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.622 AC: 42263 AN: 67960

Other (OTH) AF: 0.663 AC: 1402 AN: 2114

Alfa AF: 0.634 Hom.: 64032

Bravo AF: 0.704

Asia WGS AF: 0.672 AC: 2337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.0
DANN	Benign	0.61
PhyloP100		0.59

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: rs876982; hg19: chr19-18782377;