chr22-50549633-G-T

Variant names:

• chr22-50549633-G-T
• rs140519
• NM_138433.5:c.3390G>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_138433.5(KLHDC7B):​c.3390G>T​(p.Val1130Val) 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
• Publications: 19 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138433.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHDC7B	NM_138433.5	MANE Select	c.3390G>T	p.Val1130Val	synonymous	Exon 1 of 1	NP_612442.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHDC7B	ENST00000648057.3	MANE Select	c.3390G>T	p.Val1130Val	synonymous	Exon 1 of 1	ENSP00000497256.1
	KLHDC7B	ENST00000395676.4	TSL:6	c.1467G>T	p.Val489Val	synonymous	Exon 1 of 1	ENSP00000379034.2

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

GnomAD2 exomes AF: 0.478 AC: 99946 AN: 209046 AF XY: 0.479

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 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

African (AFR) AF: 0.206 AC: 6658 AN: 32246

American (AMR) AF: 0.467 AC: 18718 AN: 40042

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 10057 AN: 22330

East Asian (EAS) AF: 0.615 AC: 24056 AN: 39084

South Asian (SAS) AF: 0.408 AC: 31724 AN: 77748

European-Finnish (FIN) AF: 0.576 AC: 28140 AN: 48844

Middle Eastern (MID) AF: 0.388 AC: 2122 AN: 5464

European-Non Finnish (NFE) AF: 0.485 AC: 523275 AN: 1079500

Other (OTH) AF: 0.456 AC: 26321 AN: 57772

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

African (AFR) AF: 0.223 AC: 9245 AN: 41488

American (AMR) AF: 0.440 AC: 6729 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 1575 AN: 3468

East Asian (EAS) AF: 0.621 AC: 3207 AN: 5164

South Asian (SAS) AF: 0.408 AC: 1970 AN: 4826

European-Finnish (FIN) AF: 0.589 AC: 6237 AN: 10584

Middle Eastern (MID) AF: 0.342 AC: 100 AN: 292

European-Non Finnish (NFE) AF: 0.484 AC: 32885 AN: 67918

Other (OTH) AF: 0.403 AC: 848 AN: 2106

Alfa AF: 0.446 Hom.: 36158

Bravo AF: 0.403

Asia WGS AF: 0.432 AC: 1505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	5.5
DANN	Benign	0.79
PhyloP100		2.7
Mutation Taster		=100/0	polymorphism (auto)

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