19-53511584-A-G

Variant names:

• chr19-53511584-A-G
• rs37403
• XM_047439049.1:c.-1104-379A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_047439049.1(ZNF331):​c.-1104-379A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 151,966 control chromosomes in the GnomAD database, including 10,827 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 0.37 (10827 hom., cov: 32)
• Consequence: ZNF331 XM_047439049.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.649

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]

ENSG00000213777 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF331	XM_047439049.1	c.-1104-379A>G		intron_variant	Intron 1 of 11		XP_047295005.1
ZNF331	XM_047439051.1	c.-1875-379A>G		intron_variant	Intron 1 of 11		XP_047295007.1
ZNF331	XM_047439053.1	c.-2306-379A>G		intron_variant	Intron 1 of 12		XP_047295009.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000213777	ENST00000597004.1	n.279-379A>G		intron_variant	Intron 1 of 2	4
ENSG00000213777	ENST00000601966.1	n.130-379A>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56483 AN: 151850 Hom.: 10807 Cov.: 32

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.372 AC: 56544 AN: 151966 Hom.: 10827 Cov.: 32 AF XY: 0.370 AC XY: 27483 AN XY: 74282

Gnomad4 AFR AF: 0.467

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.337

Gnomad4 OTH AF: 0.355

Alfa AF: 0.354 Hom.: 1989

Bravo AF: 0.376

Asia WGS AF: 0.378 AC: 1309 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.6
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs37403; hg19: chr19-54014838;