rs7258566

Variant names:

• chr19-53509026-C-T
• rs7258566
• XM_047439049.1:c.-1104-2937C>T

Variant summary

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

The ENST00000601966.2(ENSG00000293186):​n.1162-2937C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0421 in 152,134 control chromosomes in the GnomAD database, including 183 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 0.042 (183 hom., cov: 32)
• Consequence: ENSG00000293186 ENST00000601966.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85
• Publications: 5 publications found

Genes affected

ZNF331 (HGNC:15489): (zinc finger protein 331) This gene encodes a zinc finger protein containing a KRAB (Kruppel-associated box) domain found in transcriptional repressors. This gene may be methylated and silenced in cancer cells. This gene is located within a differentially methylated region (DMR) and shows allele-specific expression in placenta. Alternative splicing and the use of alternative promoters results in multiple transcript variants encoding the same protein. [provided by RefSeq, Nov 2015]

ENSG00000293186 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000601966.2. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000293186	ENST00000597004.2	TSL:4	n.279-2937C>T		intron	N/A
	ENSG00000293186	ENST00000601966.2	TSL:3	n.1162-2937C>T		intron	N/A
	ENSG00000293186	ENST00000766785.1		n.1147-2937C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0421 AC: 6398 AN: 152016 Hom.: 182 Cov.: 32

Gnomad AFR AF: 0.0164

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0547

Gnomad ASJ AF: 0.0603

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.0909

Gnomad FIN AF: 0.0415

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0438

Gnomad OTH AF: 0.0397

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

GnomAD4 genome AF: 0.0421 AC: 6408 AN: 152134 Hom.: 183 Cov.: 32 AF XY: 0.0433 AC XY: 3222 AN XY: 74362

African (AFR) AF: 0.0164 AC: 682 AN: 41516

American (AMR) AF: 0.0550 AC: 840 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0603 AC: 209 AN: 3466

East Asian (EAS) AF: 0.135 AC: 693 AN: 5148

South Asian (SAS) AF: 0.0904 AC: 435 AN: 4814

European-Finnish (FIN) AF: 0.0415 AC: 440 AN: 10608

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0438 AC: 2978 AN: 67982

Other (OTH) AF: 0.0416 AC: 88 AN: 2114

Alfa AF: 0.0469 Hom.: 99

Bravo AF: 0.0400

Asia WGS AF: 0.112 AC: 388 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.67
DANN	Benign	0.40
PhyloP100		-1.9

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7258566;

hg19: chr19-54012280;