8-40868875-A-G

Position:

• chr8-40868875-A-G

Variant summary

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

The NM_024645.3(ZMAT4):​c.-5+28808T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,190 control chromosomes in the GnomAD database, including 3,764 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 0.22 (3764 hom., cov: 33)
• Consequence: ZMAT4 NM_024645.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZMAT4	NM_024645.3	c.-5+28808T>C		intron_variant		ENST00000297737.11	NP_078921.1
ZMAT4	NM_001135731.2	c.-5+28808T>C		intron_variant			NP_001129203.1
ZMAT4	XM_017013836.3	c.-5+28808T>C		intron_variant			XP_016869325.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZMAT4	ENST00000297737.11	c.-5+28808T>C		intron_variant		2	NM_024645.3	ENSP00000297737	P1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33424 AN: 152072 Hom.: 3752 Cov.: 33

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.0945

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.220 AC: 33463 AN: 152190 Hom.: 3764 Cov.: 33 AF XY: 0.218 AC XY: 16237 AN XY: 74418

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.0944

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.213

Alfa AF: 0.167 Hom.: 423

Bravo AF: 0.224

Asia WGS AF: 0.125 AC: 437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.24
DANN	Benign	0.39

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: rs7829127; hg19: chr8-40726394;