rs11672136

Variant names:

• chr19-57490144-T-A
• rs11672136
• NM_024691.4:c.34-3T>A

Your query was ambiguous. Multiple possible variants found:

• chr19-57490144-T-A
• chr19-57490144-T-C
• chr19-57490144-T-G

Variant summary

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

The NM_024691.4(ZNF419):​c.34-3T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 1,611,424 control chromosomes in the GnomAD database, including 114,964 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.37 (10520 hom., cov: 31)
  • Exomes 𝑓: 0.37 (104444 hom.)
• Consequence: ZNF419 NM_024691.4 splice_region, intron
• Scores: Splicing: ADA: 0.001996
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.627
• Publications: 13 publications found

Genes affected

ZNF419 (HGNC:20648): (zinc finger protein 419) 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]

ENSG00000268107 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF419	NM_024691.4	c.34-3T>A		splice_region_variant, intron_variant	Intron 1 of 4	ENST00000221735.12	NP_078967.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF419	ENST00000221735.12	c.34-3T>A		splice_region_variant, intron_variant	Intron 1 of 4	1	NM_024691.4	ENSP00000221735.7
ENSG00000268107	ENST00000601674.6	n.34-1327T>A		intron_variant	Intron 1 of 5	2		ENSP00000471625.1

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55485 AN: 151742 Hom.: 10508 Cov.: 31

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.324

GnomAD2 exomes AF: 0.413 AC: 102271 AN: 247636 AF XY: 0.409

Gnomad AFR exome AF: 0.335

Gnomad AMR exome AF: 0.551

Gnomad ASJ exome AF: 0.313

Gnomad EAS exome AF: 0.616

Gnomad FIN exome AF: 0.422

Gnomad NFE exome AF: 0.332

Gnomad OTH exome AF: 0.371

GnomAD4 exome AF: 0.371 AC: 541095 AN: 1459562 Hom.: 104444 Cov.: 33 AF XY: 0.373 AC XY: 270510 AN XY: 725940

African (AFR) AF: 0.335 AC: 11214 AN: 33440

American (AMR) AF: 0.533 AC: 23737 AN: 44570

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 7968 AN: 26094

East Asian (EAS) AF: 0.617 AC: 24458 AN: 39660

South Asian (SAS) AF: 0.509 AC: 43707 AN: 85948

European-Finnish (FIN) AF: 0.424 AC: 22623 AN: 53326

Middle Eastern (MID) AF: 0.305 AC: 1755 AN: 5760

European-Non Finnish (NFE) AF: 0.345 AC: 383412 AN: 1110478

Other (OTH) AF: 0.369 AC: 22221 AN: 60286

GnomAD4 genome AF: 0.366 AC: 55539 AN: 151862 Hom.: 10520 Cov.: 31 AF XY: 0.372 AC XY: 27615 AN XY: 74180

African (AFR) AF: 0.334 AC: 13818 AN: 41398

American (AMR) AF: 0.407 AC: 6218 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1098 AN: 3468

East Asian (EAS) AF: 0.619 AC: 3174 AN: 5124

South Asian (SAS) AF: 0.523 AC: 2506 AN: 4794

European-Finnish (FIN) AF: 0.420 AC: 4435 AN: 10556

Middle Eastern (MID) AF: 0.271 AC: 79 AN: 292

European-Non Finnish (NFE) AF: 0.343 AC: 23288 AN: 67948

Other (OTH) AF: 0.323 AC: 680 AN: 2104

Alfa AF: 0.270 Hom.: 1072

Bravo AF: 0.363

Asia WGS AF: 0.553 AC: 1919 AN: 3478

EpiCase AF: 0.320

EpiControl AF: 0.311

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.54
PhyloP100		-0.63
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0020
dbscSNV1_RF	Benign	0.078
SpliceAI score (max)		0.42		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.42		Position offset: 3

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

Other links and lift over

dbSNP: rs11672136; hg19: chr19-58001512;