rs7258566

Variant names:

• chr19-53509026-C-T
• rs7258566
• ENST00000597004.2:n.279-2937C>T

Variant summary

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

The ENST00000597004.2(ENSG00000293186):​n.279-2937C>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 ENST00000597004.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85
• Publications: 5 publications found

Genes affected

ENSG00000293186 (HGNC:):

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]

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF331	XM_047439049.1	c.-1104-2937C>T		intron_variant	Intron 1 of 11		XP_047295005.1
ZNF331	XM_047439051.1	c.-1875-2937C>T		intron_variant	Intron 1 of 11		XP_047295007.1
ZNF331	XM_047439053.1	c.-2306-2937C>T		intron_variant	Intron 1 of 12		XP_047295009.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000293186	ENST00000597004.2	n.279-2937C>T		intron_variant	Intron 1 of 4	4
ENSG00000293186	ENST00000601966.2	n.1162-2937C>T		intron_variant	Intron 2 of 3	3
ENSG00000293186	ENST00000766785.1	n.1147-2937C>T		intron_variant	Intron 2 of 4

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 v4.3

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

Other links and lift over

dbSNP: rs7258566; hg19: chr19-54012280;