8-40882173-G-A

Variant names:

• chr8-40882173-G-A
• rs4736884
• NM_024645.3:c.-5+15510C>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.-5+15510C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,056 control chromosomes in the GnomAD database, including 3,624 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 (3624 hom., cov: 32)
• Consequence: ZMAT4 NM_024645.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.163
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024645.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMAT4	NM_024645.3	MANE Select	c.-5+15510C>T		intron	N/A	NP_078921.1
	ZMAT4	NM_001135731.2		c.-5+15510C>T		intron	N/A	NP_001129203.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMAT4	ENST00000297737.11	TSL:2 MANE Select	c.-5+15510C>T		intron	N/A	ENSP00000297737.6
	ZMAT4	ENST00000315769.11	TSL:1	c.-5+15510C>T		intron	N/A	ENSP00000319785.7
	ZMAT4	ENST00000519406.5	TSL:3	c.-5+6322C>T		intron	N/A	ENSP00000428423.1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32810 AN: 151936 Hom.: 3610 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.0794

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.216 AC: 32856 AN: 152056 Hom.: 3624 Cov.: 32 AF XY: 0.215 AC XY: 15955 AN XY: 74316

African (AFR) AF: 0.233 AC: 9655 AN: 41460

American (AMR) AF: 0.250 AC: 3811 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 820 AN: 3472

East Asian (EAS) AF: 0.0792 AC: 409 AN: 5164

South Asian (SAS) AF: 0.103 AC: 496 AN: 4820

European-Finnish (FIN) AF: 0.215 AC: 2263 AN: 10542

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14766 AN: 68004

Other (OTH) AF: 0.209 AC: 442 AN: 2116

Alfa AF: 0.229 Hom.: 685

Bravo AF: 0.220

Asia WGS AF: 0.115 AC: 403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.49
DANN	Benign	0.62
PhyloP100		-0.16
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: rs4736884; hg19: chr8-40739692;