NM_138433.5:c.1687_1688insCAACCCCAGCCGCATCCCCAGCCCTAACCCCAGTCCCAACCCCAGCCCTAAGCCCAGCTCCAACTCCAGCCC

Variant names:

• chr22-50547870-C-CCATCCCCAGCCCTAACCCCAGTCCCAACCCCAGCCCTAAGCCCAGCTCCAACTCCAGCCCCAACCCCAGCCG
• rs2069749252
• NM_138433.5:c.1687_1688insCAACCCCAGCCGCATCCCCAGCCCTAACCCCAGTCCCAACCCCAGCCCTAAGCCCAGCTCCAACTCCAGCCC

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP3 BP6_Moderate

The NM_138433.5(KLHDC7B):​c.1687_1688insCAACCCCAGCCGCATCCCCAGCCCTAACCCCAGTCCCAACCCCAGCCCTAAGCCCAGCTCCAACTCCAGCCC​(p.Ala562_Leu563insProThrProAlaAlaSerProAlaLeuThrProValProThrProAlaLeuSerProAlaProThrProAla) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (9 hom., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: KLHDC7B NM_138433.5 disruptive_inframe_insertion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.356
• Publications: 0 publications found

Genes affected

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

KLHDC7B-DT (HGNC:53791): (KLHDC7B divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_138433.5
• BP6: Variant 22-50547870-C-CCATCCCCAGCCCTAACCCCAGTCCCAACCCCAGCCCTAAGCCCAGCTCCAACTCCAGCCCCAACCCCAGCCG is Benign according to our data. Variant chr22-50547870-C-CCATCCCCAGCCCTAACCCCAGTCCCAACCCCAGCCCTAAGCCCAGCTCCAACTCCAGCCCCAACCCCAGCCG is described in ClinVar as Likely_benign. ClinVar VariationId is 2653402.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHDC7B	NM_138433.5	MANE Select	c.1687_1688insCAACCCCAGCCGCATCCCCAGCCCTAACCCCAGTCCCAACCCCAGCCCTAAGCCCAGCTCCAACTCCAGCCC	p.Ala562_Leu563insProThrProAlaAlaSerProAlaLeuThrProValProThrProAlaLeuSerProAlaProThrProAla	disruptive_inframe_insertion	Exon 1 of 1	NP_612442.3	A0A3B3ISF6
	KLHDC7B-DT	NR_199716.1		n.52+1025_52+1026insCGGCTGGGGTTGGGGCTGGAGTTGGAGCTGGGCTTAGGGCTGGGGTTGGGACTGGGGTTAGGGCTGGGGATG		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHDC7B	ENST00000648057.3	MANE Select	c.1687_1688insCAACCCCAGCCGCATCCCCAGCCCTAACCCCAGTCCCAACCCCAGCCCTAAGCCCAGCTCCAACTCCAGCCC	p.Ala562_Leu563insProThrProAlaAlaSerProAlaLeuThrProValProThrProAlaLeuSerProAlaProThrProAla	disruptive_inframe_insertion	Exon 1 of 1	ENSP00000497256.1	A0A3B3ISF6
	KLHDC7B-DT	ENST00000796178.1		n.99+1025_99+1026insCGGCTGGGGTTGGGGCTGGAGTTGGAGCTGGGCTTAGGGCTGGGGTTGGGACTGGGGTTAGGGCTGGGGATG		intron	N/A
	KLHDC7B-DT	ENST00000796179.1		n.30+953_30+954insCGGCTGGGGTTGGGGCTGGAGTTGGAGCTGGGCTTAGGGCTGGGGTTGGGACTGGGGTTAGGGCTGGGGATG		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000177 AC: 22 AN: 124636 Hom.: 9 Cov.: 23

Gnomad AFR AF: 0.0000300

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000340

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000744

Gnomad SAS AF: 0.000520

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000207

Gnomad OTH AF: 0.00

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000176 AC: 22 AN: 124710 Hom.: 9 Cov.: 23 AF XY: 0.000232 AC XY: 14 AN XY: 60224

African (AFR) AF: 0.0000299 AC: 1 AN: 33406

American (AMR) AF: 0.000340 AC: 4 AN: 11756

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3094

East Asian (EAS) AF: 0.000746 AC: 3 AN: 4022

South Asian (SAS) AF: 0.000522 AC: 2 AN: 3832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8012

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.000207 AC: 12 AN: 57922

Other (OTH) AF: 0.00 AC: 0 AN: 1734

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.36

Splicing

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

Other links and lift over

dbSNP: rs2069749252; hg19: chr22-50986299;