chr7-112318211-A-G

Variant names:

• chr7-112318211-A-G
• rs138489628
• NM_021994.3:c.495A>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_021994.3(ZNF277):​c.495A>G​(p.Glu165Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00202 in 1,613,446 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (21 hom.)
• Consequence: ZNF277 NM_021994.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.772
• Publications: 1 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 7-112318211-A-G is Benign according to our data. Variant chr7-112318211-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2657948.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.772 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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.495A>G	p.Glu165Glu	synonymous	Exon 5 of 12	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.495A>G	p.Glu165Glu	synonymous	Exon 5 of 12	ENSP00000354501.3	Q9NRM2
	ZNF277	ENST00000450657.1	TSL:1	c.495A>G	p.Glu165Glu	synonymous	Exon 5 of 7	ENSP00000402292.1	G5E9M4
	ZNF277	ENST00000361946.8	TSL:1	n.*338A>G		non_coding_transcript_exon	Exon 5 of 12	ENSP00000355043.4	E7EW13

Frequencies

GnomAD3 genomes AF: 0.00166 AC: 252 AN: 152070 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0119

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00174

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.00216 AC: 543 AN: 251192 AF XY: 0.00224

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0116

Gnomad NFE exome AF: 0.00247

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.00206 AC: 3015 AN: 1461258 Hom.: 21 Cov.: 30 AF XY: 0.00201 AC XY: 1463 AN XY: 726926

African (AFR) AF: 0.000179 AC: 6 AN: 33474

American (AMR) AF: 0.0000224 AC: 1 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86224

European-Finnish (FIN) AF: 0.00968 AC: 517 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00218 AC: 2420 AN: 1111496

Other (OTH) AF: 0.00116 AC: 70 AN: 60370

GnomAD4 genome AF: 0.00166 AC: 252 AN: 152188 Hom.: 3 Cov.: 32 AF XY: 0.00208 AC XY: 155 AN XY: 74400

African (AFR) AF: 0.000144 AC: 6 AN: 41566

American (AMR) AF: 0.0000655 AC: 1 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.0119 AC: 126 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00174 AC: 118 AN: 67974

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.00157 Hom.: 1

Bravo AF: 0.000941

EpiCase AF: 0.00180

EpiControl AF: 0.00190

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	5.8
DANN	Benign	0.62
PhyloP100		0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs138489628; hg19: chr7-111958266;