chr19-12611518-A-C

Variant names:

• chr19-12611518-A-C
• rs2861405
• NM_153358.3:c.3+436A>C

Variant summary

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

The NM_153358.3(ZNF791):​c.3+436A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 151,954 control chromosomes in the GnomAD database, including 34,137 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 0.66 (34137 hom., cov: 31)
• Consequence: ZNF791 NM_153358.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.593
• Publications: 8 publications found

Genes affected

ZNF791 (HGNC:26895): (zinc finger protein 791) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF490 (HGNC:23705): (zinc finger protein 490) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153358.3. 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
	ZNF791	NM_153358.3	MANE Select	c.3+436A>C		intron	N/A	NP_699189.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF791	ENST00000343325.9	TSL:1 MANE Select	c.3+436A>C		intron	N/A	ENSP00000342974.4
	ZNF791	ENST00000446165.2	TSL:1	c.3+436A>C		intron	N/A	ENSP00000412981.1
	ZNF791	ENST00000600752.1	TSL:2	c.-198+436A>C		intron	N/A	ENSP00000471179.1

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100179 AN: 151836 Hom.: 34082 Cov.: 31

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.743

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.660

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

GnomAD4 genome AF: 0.660 AC: 100285 AN: 151954 Hom.: 34137 Cov.: 31 AF XY: 0.646 AC XY: 47970 AN XY: 74264

African (AFR) AF: 0.738 AC: 30604 AN: 41444

American (AMR) AF: 0.557 AC: 8494 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.743 AC: 2578 AN: 3470

East Asian (EAS) AF: 0.182 AC: 943 AN: 5170

South Asian (SAS) AF: 0.425 AC: 2047 AN: 4818

European-Finnish (FIN) AF: 0.619 AC: 6524 AN: 10538

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.690 AC: 46894 AN: 67962

Other (OTH) AF: 0.664 AC: 1400 AN: 2110

Alfa AF: 0.675 Hom.: 92296

Bravo AF: 0.660

Asia WGS AF: 0.359 AC: 1255 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	2.8
DANN	Benign	0.33
PhyloP100		-0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2861405; hg19: chr19-12722332;