chr7-128877201-C-A

Variant names:

• chr7-128877201-C-A
• rs1202619970
• NM_001366122.1:c.4729G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001366122.1(KCP):​c.4729G>T​(p.Val1577Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000751 in 1,331,000 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1577M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: KCP NM_001366122.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.67
• Publications: 0 publications found

Genes affected

KCP (HGNC:17585): (kielin cysteine rich BMP regulator) Predicted to act upstream of or within hematopoietic progenitor cell differentiation and positive regulation of BMP signaling pathway. Predicted to be located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20007908).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCP	NM_001366122.1	c.4729G>T	p.Val1577Leu	missense_variant	Exon 40 of 40	ENST00000610776.5	NP_001353051.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCP	ENST00000610776.5	c.4729G>T	p.Val1577Leu	missense_variant	Exon 40 of 40	5	NM_001366122.1	ENSP00000479679.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.51e-7 AC: 1 AN: 1331000 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 650596

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 28776

American (AMR) AF: 0.00 AC: 0 AN: 21740

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21010

East Asian (EAS) AF: 0.00 AC: 0 AN: 35116

South Asian (SAS) AF: 0.00 AC: 0 AN: 68536

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46566

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4978

European-Non Finnish (NFE) AF: 9.53e-7 AC: 1 AN: 1049342

Other (OTH) AF: 0.00 AC: 0 AN: 54936

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	21
DANN	Benign	0.70
DEOGEN2	Benign	0.0026	T;.;T
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.85	T;T;T
MetaRNN	Benign	0.20	T;T;T
PhyloP100		2.7
PrimateAI	Uncertain	0.51	T
Sift4G	Benign	0.50	T;T;T
Vest4		0.20
MVP		0.16
GERP RS		4.3
Varity_R		0.068
gMVP		0.24
Mutation Taster		=100/0	polymorphism

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: rs1202619970; hg19: chr7-128517255;