rs2295715

Variant names:

• chr10-101067471-G-A
• rs2295715
• ENST00000465807.1:n.474G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-101067471-G-A
• chr10-101067471-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000465807.1(KAZALD1):​n.474G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 368,266 control chromosomes in the GnomAD database, including 6,595 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 0.21 (3628 hom., cov: 33)
  • Exomes 𝑓: 0.16 (2967 hom.)
• Consequence: KAZALD1 ENST00000465807.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.22
• Publications: 3 publications found

Genes affected

KAZALD1 (HGNC:25460): (Kazal type serine peptidase inhibitor domain 1) This gene encodes a secreted member of the insulin growth factor-binding protein (IGFBP) superfamily. The protein contains an insulin growth factor-binding domain in its N-terminal region, a Kazal-type serine protease inhibitor and follistatin-like domain in its central region, and an immunoglobulin-like domain in its C-terminal region. Studies of the mouse ortholog suggest that this protein may function in bone development and bone regeneration. This gene is hypomethylated and over-expressed in high-grade glioma compared to low-grade glioma, and thus the hypomethylated gene may be associated with cell proliferation and the shorter survival of patients with high-grade glioma. It is also one of numerous genes found to be deleted in a novel 5.54 Mb interstitial deletion, which is associated with multiple congenital anomalies. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ENSG00000288844 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KAZALD1	NR_135067.2	n.778G>A		non_coding_transcript_exon_variant	Exon 5 of 5
KAZALD1	NR_135068.2	n.390G>A		non_coding_transcript_exon_variant	Exon 2 of 2
KAZALD1	XR_246107.4	n.2945G>A		non_coding_transcript_exon_variant	Exon 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KAZALD1	ENST00000465807.1	n.474G>A		non_coding_transcript_exon_variant	Exon 2 of 2	1
KAZALD1	ENST00000477267.1	n.677G>A		non_coding_transcript_exon_variant	Exon 5 of 5	5
ENSG00000288844	ENST00000686265.2	n.547C>T		non_coding_transcript_exon_variant	Exon 1 of 1
ENSG00000288844	ENST00000799115.1	n.142+62C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31310 AN: 152090 Hom.: 3621 Cov.: 33

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.0842

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.217

GnomAD4 exome AF: 0.157 AC: 33834 AN: 216058 Hom.: 2967 Cov.: 0 AF XY: 0.148 AC XY: 17747 AN XY: 119918

African (AFR) AF: 0.288 AC: 1638 AN: 5696

American (AMR) AF: 0.238 AC: 3258 AN: 13714

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 687 AN: 4984

East Asian (EAS) AF: 0.224 AC: 1857 AN: 8292

South Asian (SAS) AF: 0.0917 AC: 4137 AN: 45130

European-Finnish (FIN) AF: 0.142 AC: 1295 AN: 9116

Middle Eastern (MID) AF: 0.184 AC: 413 AN: 2240

European-Non Finnish (NFE) AF: 0.162 AC: 18860 AN: 116592

Other (OTH) AF: 0.164 AC: 1689 AN: 10294

GnomAD4 genome AF: 0.206 AC: 31342 AN: 152208 Hom.: 3628 Cov.: 33 AF XY: 0.203 AC XY: 15109 AN XY: 74414

African (AFR) AF: 0.298 AC: 12370 AN: 41532

American (AMR) AF: 0.238 AC: 3638 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 486 AN: 3468

East Asian (EAS) AF: 0.230 AC: 1192 AN: 5174

South Asian (SAS) AF: 0.0847 AC: 409 AN: 4830

European-Finnish (FIN) AF: 0.135 AC: 1428 AN: 10588

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11150 AN: 68004

Other (OTH) AF: 0.216 AC: 456 AN: 2114

Alfa AF: 0.180 Hom.: 8830

Bravo AF: 0.221

Asia WGS AF: 0.151 AC: 524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.17
DANN	Benign	0.90
PhyloP100		-3.2

Splicing

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

Other links and lift over

dbSNP: rs2295715; hg19: chr10-102827228;