4-339807-C-G

Variant names:

• chr4-339807-C-G
• rs11727981
• NM_003441.4:c.3+1821C>G

Variant summary

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

The NM_003441.4(ZNF141):​c.3+1821C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 152,084 control chromosomes in the GnomAD database, including 14,851 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 0.43 (14851 hom., cov: 33)
• Consequence: ZNF141 NM_003441.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64
• Publications: 1 publications found

Genes affected

ZNF141 (HGNC:12926): (zinc finger protein 141) The protein encoded by this gene is a zinc finger protein that may be a tumor suppressor. Defects in this gene have been associated with autosomal recessive postaxial polydactyly type A. [provided by RefSeq, Jan 2017]

ZNF141 Gene-Disease associations (from GenCC):

• postaxial polydactyly type A

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• polydactyly, postaxial, type A6

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003441.4. 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
	ZNF141	NM_003441.4	MANE Select	c.3+1821C>G		intron	N/A	NP_003432.1	Q15928
	ZNF141	NM_001348277.2		c.-3+1821C>G		intron	N/A	NP_001335206.1	Q4W5N2
	ZNF141	NM_001348278.2		c.3+1821C>G		intron	N/A	NP_001335207.1	D6RIY0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF141	ENST00000240499.8	TSL:1 MANE Select	c.3+1821C>G		intron	N/A	ENSP00000240499.7	Q15928
	ZNF141	ENST00000512994.5	TSL:1	c.3+1821C>G		intron	N/A	ENSP00000425799.1	D6RIY0
	ZNF141	ENST00000503699.1	TSL:1	n.154+1821C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65800 AN: 151966 Hom.: 14835 Cov.: 33

Gnomad AFR AF: 0.565

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.433 AC: 65846 AN: 152084 Hom.: 14851 Cov.: 33 AF XY: 0.433 AC XY: 32160 AN XY: 74344

African (AFR) AF: 0.565 AC: 23439 AN: 41460

American (AMR) AF: 0.339 AC: 5174 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 1586 AN: 3470

East Asian (EAS) AF: 0.315 AC: 1632 AN: 5180

South Asian (SAS) AF: 0.426 AC: 2055 AN: 4824

European-Finnish (FIN) AF: 0.428 AC: 4519 AN: 10568

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.384 AC: 26090 AN: 67982

Other (OTH) AF: 0.425 AC: 900 AN: 2116

Alfa AF: 0.400 Hom.: 1522

Bravo AF: 0.433

Asia WGS AF: 0.387 AC: 1346 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.87
DANN	Benign	0.32
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11727981; hg19: chr4-333596;