rs2137277

chr8-40877143-A-Gchr8-40877143-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.-5+20540T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,144 control chromosomes in the GnomAD database, including 3,382 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 0.21 (3382 hom., cov: 32)
• Consequence: ZMAT4 NM_024645.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZMAT4	NM_024645.3	c.-5+20540T>C		intron_variant		ENST00000297737.11
ZMAT4	NM_001135731.2	c.-5+20540T>C		intron_variant
ZMAT4	XM_017013836.3	c.-5+20540T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZMAT4	ENST00000297737.11	c.-5+20540T>C		intron_variant		2	NM_024645.3	P1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31640 AN: 152026 Hom.: 3365 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.0795

Gnomad SAS AF: 0.0979

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.208 AC: 31691 AN: 152144 Hom.: 3382 Cov.: 32 AF XY: 0.207 AC XY: 15397 AN XY: 74374

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.0793

Gnomad4 SAS AF: 0.0972

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.201

Alfa AF: 0.212 Hom.: 783

Bravo AF: 0.213

Asia WGS AF: 0.115 AC: 401 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.026
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: rs2137277; hg19: chr8-40734662;