chr19-53511584-A-G

Variant names:

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

Variant summary

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

The ENST00000601966.2(ENSG00000293186):​n.1162-379A>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: ENSG00000293186 ENST00000601966.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.649
• Publications: 1 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.462 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.279-379A>G		intron	N/A
	ENSG00000293186	ENST00000601966.2	TSL:3	n.1162-379A>G		intron	N/A
	ENSG00000293186	ENST00000766785.1		n.1147-379A>G		intron	N/A

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

African (AFR) AF: 0.467 AC: 19354 AN: 41442

American (AMR) AF: 0.312 AC: 4759 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1284 AN: 3470

East Asian (EAS) AF: 0.425 AC: 2196 AN: 5168

South Asian (SAS) AF: 0.338 AC: 1627 AN: 4816

European-Finnish (FIN) AF: 0.304 AC: 3205 AN: 10548

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.337 AC: 22913 AN: 67950

Other (OTH) AF: 0.355 AC: 749 AN: 2112

Alfa AF: 0.351 Hom.: 14432

Bravo AF: 0.376

Asia WGS AF: 0.378 AC: 1309 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.6
DANN	Benign	0.44
PhyloP100		-0.65

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: rs37403;

hg19: chr19-54014838;