rs4765127

Variant names:

• chr12-123975620-G-T
• rs4765127
• NM_152437.3:c.-757+1600G>T

Variant summary

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

The NM_152437.3(ZNF664):​c.-757+1600G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 151,812 control chromosomes in the GnomAD database, including 8,103 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 0.32 (8103 hom., cov: 31)
• Consequence: ZNF664 NM_152437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127
• Publications: 92 publications found

Genes affected

ZNF664 (HGNC:25406): (zinc finger protein 664) 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, DNA-templated. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF664-RFLNA (HGNC:):

RFLNA (HGNC:27051): (refilin A) Predicted to enable filamin binding activity. Predicted to be involved in several processes, including actin filament bundle organization; negative regulation of bone mineralization involved in bone maturation; and negative regulation of chondrocyte development. Predicted to be located in cytoplasm. Predicted to be active in actin filament bundle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF664	NM_152437.3	c.-757+1600G>T		intron_variant	Intron 2 of 4	ENST00000337815.9	NP_689650.1
ZNF664	NM_001204298.2	c.-754+1600G>T		intron_variant	Intron 2 of 4		NP_001191227.1
ZNF664-RFLNA	NM_001204299.3	c.-234+1600G>T		intron_variant	Intron 2 of 4		NP_001191228.1
ZNF664-RFLNA	NM_001347902.2	c.-234+1600G>T		intron_variant	Intron 2 of 4		NP_001334831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF664	ENST00000337815.9	c.-757+1600G>T		intron_variant	Intron 2 of 4	1	NM_152437.3	ENSP00000337320.4

Frequencies

GnomAD3 genomes AF: 0.323 AC: 49029 AN: 151694 Hom.: 8097 Cov.: 31

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.0934

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.340

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

GnomAD4 genome AF: 0.323 AC: 49069 AN: 151812 Hom.: 8103 Cov.: 31 AF XY: 0.315 AC XY: 23407 AN XY: 74200

African (AFR) AF: 0.357 AC: 14757 AN: 41344

American (AMR) AF: 0.296 AC: 4524 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1353 AN: 3460

East Asian (EAS) AF: 0.0934 AC: 483 AN: 5170

South Asian (SAS) AF: 0.217 AC: 1045 AN: 4822

European-Finnish (FIN) AF: 0.273 AC: 2877 AN: 10540

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.337 AC: 22875 AN: 67898

Other (OTH) AF: 0.337 AC: 709 AN: 2104

Alfa AF: 0.328 Hom.: 9770

Bravo AF: 0.329

Asia WGS AF: 0.213 AC: 741 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.8
DANN	Benign	0.67
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

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: rs4765127; hg19: chr12-124460167; COSMIC: COSV53020352; COSMIC: COSV53020352;