7-128877099-C-G

Variant names:

• chr7-128877099-C-G
• rs1323884628
• NM_001366122.1:c.4831G>C

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.4831G>C​(p.Asp1611His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000732 in 1,366,458 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/12 in silico tools predict 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. D1611N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: KCP NM_001366122.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860
• 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=0.10948339).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCP	NM_001366122.1	c.4831G>C	p.Asp1611His	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.4831G>C	p.Asp1611His	missense_variant	Exon 40 of 40	5	NM_001366122.1	ENSP00000479679.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.32e-7 AC: 1 AN: 1366458 Hom.: 0 Cov.: 32 AF XY: 0.00000149 AC XY: 1 AN XY: 673210

African (AFR) AF: 0.00 AC: 0 AN: 29448

American (AMR) AF: 0.00 AC: 0 AN: 24732

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23394

East Asian (EAS) AF: 0.00 AC: 0 AN: 35432

South Asian (SAS) AF: 0.00 AC: 0 AN: 74252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47976

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5428

European-Non Finnish (NFE) AF: 9.35e-7 AC: 1 AN: 1069252

Other (OTH) AF: 0.00 AC: 0 AN: 56544

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.0055	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	16
DANN	Benign	0.71
DEOGEN2	Benign	0.016	T;.;T
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.77	T;T;T
MetaRNN	Benign	0.11	T;T;T
PhyloP100		0.086
PrimateAI	Benign	0.39	T
Sift4G	Pathogenic	0.0	D;D;D
Vest4		0.087
MVP		0.31
GERP RS		3.5
Varity_R		0.047
gMVP		0.41
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: rs1323884628; hg19: chr7-128517153;