rs1449984619

Variant names:

• chr7-112286869-C-A
• rs1449984619
• NM_021994.3:c.92-4C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-112286869-C-A
• chr7-112286869-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_021994.3(ZNF277):​c.92-4C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 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 0.0 (0 hom., cov: 12)
  • Exomes 𝑓: 0.00020 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF277 NM_021994.3 splice_region, intron
• Scores: Splicing: ADA: 0.00003915
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0170
• Publications: 0 publications found

Genes affected

ZNF277 (HGNC:13070): (zinc finger protein 277) Predicted to enable RNA polymerase II cis-regulatory region sequence-specific DNA binding activity and metal ion binding activity. Predicted to act upstream of or within cellular response to hydrogen peroxide and regulation of cellular senescence. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021994.3. 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
	ZNF277	NM_021994.3	MANE Select	c.92-4C>A		splice_region intron	N/A	NP_068834.2	Q9NRM2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF277	ENST00000361822.8	TSL:1 MANE Select	c.92-4C>A		splice_region intron	N/A	ENSP00000354501.3	Q9NRM2
	ZNF277	ENST00000450657.1	TSL:1	c.92-4C>A		splice_region intron	N/A	ENSP00000402292.1	G5E9M4
	ZNF277	ENST00000361946.8	TSL:1	n.92-8C>A		splice_region intron	N/A	ENSP00000355043.4	E7EW13

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 68302 Hom.: 0 Cov.: 12

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000200 AC: 178 AN: 891586 Hom.: 0 Cov.: 30 AF XY: 0.000199 AC XY: 90 AN XY: 452134

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000160 AC: 2 AN: 12476

American (AMR) AF: 0.0000923 AC: 3 AN: 32516

Ashkenazi Jewish (ASJ) AF: 0.000109 AC: 2 AN: 18334

East Asian (EAS) AF: 0.0000717 AC: 2 AN: 27900

South Asian (SAS) AF: 0.0000381 AC: 2 AN: 52466

European-Finnish (FIN) AF: 0.0000700 AC: 3 AN: 42872

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3520

European-Non Finnish (NFE) AF: 0.000238 AC: 158 AN: 664950

Other (OTH) AF: 0.000164 AC: 6 AN: 36552

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 68316 Hom.: 0 Cov.: 12 AF XY: 0.00 AC XY: 0 AN XY: 32902

African (AFR) AF: 0.00 AC: 0 AN: 9458

American (AMR) AF: 0.00 AC: 0 AN: 5960

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2050

East Asian (EAS) AF: 0.00 AC: 0 AN: 2844

South Asian (SAS) AF: 0.00 AC: 0 AN: 2116

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4790

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 124

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 39594

Other (OTH) AF: 0.00 AC: 0 AN: 930

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.9
DANN	Benign	0.70
PhyloP100		-0.017
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000039
dbscSNV1_RF	Benign	0.0
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: rs1449984619; hg19: chr7-111926924;