rs868586

chr8-40847332-A-Gchr8-40847332-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024645.3(ZMAT4):c.-4-21652T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 152,026 control chromosomes in the GnomAD database, including 24,791 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 0.56 (24791 hom., cov: 32)
• Consequence: ZMAT4 NM_024645.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56

Genes affected

ZMAT4 (HGNC:25844): (zinc finger matrin-type 4) Enables identical protein binding activity. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZMAT4	NM_024645.3	c.-4-21652T>C		intron_variant		ENST00000297737.11
ZMAT4	NM_001135731.2	c.-4-21652T>C		intron_variant
ZMAT4	XM_017013836.3	c.-4-21652T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZMAT4	ENST00000297737.11	c.-4-21652T>C		intron_variant		2	NM_024645.3	P1

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85233 AN: 151908 Hom.: 24734 Cov.: 32

Gnomad AFR AF: 0.692

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.528

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

GnomAD4 genome AF: 0.561 AC: 85360 AN: 152026 Hom.: 24791 Cov.: 32 AF XY: 0.562 AC XY: 41771 AN XY: 74292

Gnomad4 AFR AF: 0.693

Gnomad4 AMR AF: 0.550

Gnomad4 ASJ AF: 0.501

Gnomad4 EAS AF: 0.203

Gnomad4 SAS AF: 0.549

Gnomad4 FIN AF: 0.559

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.528

Alfa AF: 0.515 Hom.: 25657

Bravo AF: 0.562

Asia WGS AF: 0.404 AC: 1406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.34
Dann	Benign	0.27

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

Publications

LitVar

Other links and lift over

dbSNP: rs868586; hg19: chr8-40704851;