chr7-116826029-T-C

Variant names:

• chr7-116826029-T-C
• rs28167
• ENST00000464223.5:c.-29+14927T>C

Variant summary

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

The ENST00000464223.5(CAPZA2):​c.-29+14927T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 152,032 control chromosomes in the GnomAD database, including 28,518 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 0.60 (28518 hom., cov: 31)
• Consequence: CAPZA2 ENST00000464223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.875
• Publications: 3 publications found

Genes affected

CAPZA2 (HGNC:1490): (capping actin protein of muscle Z-line subunit alpha 2) The protein encoded by this gene is a member of the F-actin capping protein alpha subunit family. It is the alpha subunit of the barbed-end actin binding protein Cap Z. By capping the barbed end of actin filaments, Cap Z regulates the growth of the actin filaments at the barbed end. [provided by RefSeq, Jul 2008]

CAPZA2 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

LOC124901731 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124901731	XR_007060489.1	n.84-9522T>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPZA2	ENST00000464223.5	c.-29+14927T>C		intron_variant	Intron 1 of 3	1		ENSP00000420640.1
CAPZA2	ENST00000484325.1	c.-189+14927T>C		intron_variant	Intron 1 of 4	1		ENSP00000418262.1

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91564 AN: 151914 Hom.: 28532 Cov.: 31

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.710

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.901

Gnomad SAS AF: 0.816

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.610

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

GnomAD4 genome AF: 0.602 AC: 91578 AN: 152032 Hom.: 28518 Cov.: 31 AF XY: 0.609 AC XY: 45243 AN XY: 74298

African (AFR) AF: 0.458 AC: 18975 AN: 41468

American (AMR) AF: 0.626 AC: 9564 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.720 AC: 2497 AN: 3470

East Asian (EAS) AF: 0.902 AC: 4659 AN: 5164

South Asian (SAS) AF: 0.814 AC: 3921 AN: 4818

European-Finnish (FIN) AF: 0.670 AC: 7058 AN: 10540

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.629 AC: 42787 AN: 67988

Other (OTH) AF: 0.610 AC: 1285 AN: 2108

Alfa AF: 0.622 Hom.: 14770

Bravo AF: 0.588

Asia WGS AF: 0.827 AC: 2874 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.43
PhyloP100		-0.88

Splicing

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

Other links and lift over

dbSNP: rs28167; hg19: chr7-116466083;