rs868586

Variant names:

• chr8-40847332-A-G
• rs868586
• NM_024645.3:c.-4-21652T>C

Your query was ambiguous. Multiple possible variants found:

• chr8-40847332-A-G
• chr8-40847332-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZMAT4	NM_024645.3	c.-4-21652T>C		intron_variant	Intron 1 of 6	ENST00000297737.11	NP_078921.1
ZMAT4	NM_001135731.2	c.-4-21652T>C		intron_variant	Intron 1 of 5		NP_001129203.1
ZMAT4	XM_017013836.3	c.-4-21652T>C		intron_variant	Intron 1 of 5		XP_016869325.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMAT4	ENST00000297737.11	c.-4-21652T>C		intron_variant	Intron 1 of 6	2	NM_024645.3	ENSP00000297737.6

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

African (AFR) AF: 0.693 AC: 28727 AN: 41464

American (AMR) AF: 0.550 AC: 8403 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1738 AN: 3470

East Asian (EAS) AF: 0.203 AC: 1047 AN: 5160

South Asian (SAS) AF: 0.549 AC: 2640 AN: 4810

European-Finnish (FIN) AF: 0.559 AC: 5895 AN: 10554

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.518 AC: 35240 AN: 67980

Other (OTH) AF: 0.528 AC: 1108 AN: 2100

Alfa AF: 0.522 Hom.: 33973

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
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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: rs868586; hg19: chr8-40704851;