rs2640201

Variant names:

• chr19-23530476-C-G
• rs2640201
• ENST00000601935.5:c.227-2462G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-23530476-C-G
• chr19-23530476-C-T

Variant summary

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

The ENST00000601935.5(ZNF675):​c.227-2462G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 151,946 control chromosomes in the GnomAD database, including 22,331 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 0.54 (22331 hom., cov: 32)
• Consequence: ZNF675 ENST00000601935.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.916
• Publications: 2 publications found

Genes affected

ZNF675 (HGNC:30768): (zinc finger protein 675) Enables ubiquitin protein ligase binding activity. Involved in several processes, including negative regulation of osteoclast differentiation; negative regulation of signal transduction; and regulation of transcription, DNA-templated. Located in nucleus and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

LOC105372337 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105372337	XR_936485.3	n.1148+1055G>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF675	ENST00000601935.5	c.227-2462G>C		intron_variant	Intron 3 of 4	1		ENSP00000469379.1

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81445 AN: 151828 Hom.: 22308 Cov.: 32

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.657

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.490

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

GnomAD4 genome AF: 0.537 AC: 81522 AN: 151946 Hom.: 22331 Cov.: 32 AF XY: 0.540 AC XY: 40090 AN XY: 74276

African (AFR) AF: 0.628 AC: 26009 AN: 41424

American (AMR) AF: 0.560 AC: 8558 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.434 AC: 1503 AN: 3466

East Asian (EAS) AF: 0.657 AC: 3380 AN: 5144

South Asian (SAS) AF: 0.532 AC: 2559 AN: 4806

European-Finnish (FIN) AF: 0.507 AC: 5359 AN: 10576

Middle Eastern (MID) AF: 0.397 AC: 116 AN: 292

European-Non Finnish (NFE) AF: 0.479 AC: 32520 AN: 67944

Other (OTH) AF: 0.489 AC: 1030 AN: 2108

Alfa AF: 0.349 Hom.: 852

Bravo AF: 0.540

Asia WGS AF: 0.537 AC: 1868 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.4
DANN	Benign	0.38
PhyloP100		-0.92
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2640201; hg19: chr19-23713278;