chr22-50549633-G-T

Position:

• chr22-50549633-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_138433.5(KLHDC7B):​c.3390G>T​(p.Val1130=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 1,555,092 control chromosomes in the GnomAD database, including 177,356 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 0.42 (14423 hom., cov: 34)
  • Exomes 𝑓: 0.48 (162933 hom.)
• Consequence: KLHDC7B NM_138433.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.71

Genes affected

KLHDC7B (HGNC:25145): (kelch domain containing 7B)

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=2.71 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHDC7B	NM_138433.5	c.3390G>T	p.Val1130=	synonymous_variant	1/1	ENST00000648057.3	NP_612442.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHDC7B	ENST00000648057.3	c.3390G>T	p.Val1130=	synonymous_variant	1/1		NM_138433.5	ENSP00000497256	P3
KLHDC7B	ENST00000395676.4	c.1467G>T	p.Val489=	synonymous_variant	1/1			ENSP00000379034	A2

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63342 AN: 151942 Hom.: 14418 Cov.: 34

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.405

GnomAD3 exomes AF: 0.478 AC: 99946 AN: 209046 Hom.: 24748 AF XY: 0.479 AC XY: 53545 AN XY: 111882

Gnomad AFR exome AF: 0.216

Gnomad AMR exome AF: 0.472

Gnomad ASJ exome AF: 0.467

Gnomad EAS exome AF: 0.629

Gnomad SAS exome AF: 0.407

Gnomad FIN exome AF: 0.589

Gnomad NFE exome AF: 0.492

Gnomad OTH exome AF: 0.477

GnomAD4 exome AF: 0.478 AC: 671071 AN: 1403030 Hom.: 162933 Cov.: 74 AF XY: 0.476 AC XY: 328499 AN XY: 690210

Gnomad4 AFR exome AF: 0.206

Gnomad4 AMR exome AF: 0.467

Gnomad4 ASJ exome AF: 0.450

Gnomad4 EAS exome AF: 0.615

Gnomad4 SAS exome AF: 0.408

Gnomad4 FIN exome AF: 0.576

Gnomad4 NFE exome AF: 0.485

Gnomad4 OTH exome AF: 0.456

GnomAD4 genome AF: 0.417 AC: 63357 AN: 152062 Hom.: 14423 Cov.: 34 AF XY: 0.423 AC XY: 31451 AN XY: 74334

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.440

Gnomad4 ASJ AF: 0.454

Gnomad4 EAS AF: 0.621

Gnomad4 SAS AF: 0.408

Gnomad4 FIN AF: 0.589

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.403

Alfa AF: 0.461 Hom.: 19293

Bravo AF: 0.403

Asia WGS AF: 0.432 AC: 1505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	5.5
DANN	Benign	0.79

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: rs140519; hg19: chr22-50988062; COSMIC: COSV67464203; COSMIC: COSV67464203;