rs1690625

Variant names:

• chr10-31006892-C-G
• rs1690625
• NM_001143768.2:c.-249-22466G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-31006892-C-G
• chr10-31006892-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001143768.2(ZNF438):​c.-249-22466G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 151,256 control chromosomes in the GnomAD database, including 42,321 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 0.74 (42321 hom., cov: 29)
• Consequence: ZNF438 NM_001143768.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.996
• Publications: 3 publications found

Genes affected

ZNF438 (HGNC:21029): (zinc finger protein 438) Enables DNA-binding transcription factor activity. Involved in negative regulation of transcription, DNA-templated. Located in cytosol and nucleoplasm. [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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143768.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF438	NM_001143768.2	MANE Select	c.-249-22466G>C		intron	N/A	NP_001137240.1	Q7Z4V0-1
	ZNF438	NM_001143766.2		c.-378-22466G>C		intron	N/A	NP_001137238.1	Q7Z4V0-1
	ZNF438	NM_001143767.2		c.-192+24941G>C		intron	N/A	NP_001137239.1	Q7Z4V0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF438	ENST00000436087.7	TSL:5 MANE Select	c.-249-22466G>C		intron	N/A	ENSP00000406934.2	Q7Z4V0-1
	ZNF438	ENST00000413025.5	TSL:5	c.-192+24941G>C		intron	N/A	ENSP00000387546.1	Q7Z4V0-1
	ZNF438	ENST00000442986.5	TSL:5	c.-330-22466G>C		intron	N/A	ENSP00000412363.1	Q7Z4V0-1

Frequencies

GnomAD3 genomes AF: 0.743 AC: 112226 AN: 151142 Hom.: 42278 Cov.: 29

Gnomad AFR AF: 0.828

Gnomad AMI AF: 0.771

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.786

Gnomad MID AF: 0.752

Gnomad NFE AF: 0.732

Gnomad OTH AF: 0.720

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

GnomAD4 genome AF: 0.743 AC: 112330 AN: 151256 Hom.: 42321 Cov.: 29 AF XY: 0.742 AC XY: 54749 AN XY: 73824

African (AFR) AF: 0.828 AC: 34157 AN: 41234

American (AMR) AF: 0.713 AC: 10830 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2245 AN: 3468

East Asian (EAS) AF: 0.400 AC: 2050 AN: 5130

South Asian (SAS) AF: 0.604 AC: 2893 AN: 4788

European-Finnish (FIN) AF: 0.786 AC: 8146 AN: 10364

Middle Eastern (MID) AF: 0.750 AC: 219 AN: 292

European-Non Finnish (NFE) AF: 0.732 AC: 49579 AN: 67774

Other (OTH) AF: 0.719 AC: 1508 AN: 2096

Alfa AF: 0.737 Hom.: 4878

Bravo AF: 0.742

Asia WGS AF: 0.547 AC: 1903 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.36
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1690625; hg19: chr10-31295821;