chr12-123984025-G-C

Variant names:

• chr12-123984025-G-C
• rs7978610
• NM_152437.3:c.-756-4018G>C

Variant summary

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

The NM_152437.3(ZNF664):​c.-756-4018G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 152,090 control chromosomes in the GnomAD database, including 8,075 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 (8075 hom., cov: 32)
• Consequence: ZNF664 NM_152437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05
• Publications: 22 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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF664	NM_152437.3	c.-756-4018G>C		intron_variant	Intron 2 of 4	ENST00000337815.9	NP_689650.1
ZNF664	NM_001204298.2	c.-753-4021G>C		intron_variant	Intron 2 of 4		NP_001191227.1
ZNF664-RFLNA	NM_001204299.3	c.-234+10005G>C		intron_variant	Intron 2 of 4		NP_001191228.1
ZNF664-RFLNA	NM_001347902.2	c.-234+10005G>C		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.-756-4018G>C		intron_variant	Intron 2 of 4	1	NM_152437.3	ENSP00000337320.4

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48973 AN: 151972 Hom.: 8069 Cov.: 32

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.0931

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.322 AC: 49013 AN: 152090 Hom.: 8075 Cov.: 32 AF XY: 0.315 AC XY: 23388 AN XY: 74350

African (AFR) AF: 0.355 AC: 14703 AN: 41438

American (AMR) AF: 0.296 AC: 4519 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1354 AN: 3472

East Asian (EAS) AF: 0.0931 AC: 483 AN: 5186

South Asian (SAS) AF: 0.216 AC: 1040 AN: 4816

European-Finnish (FIN) AF: 0.272 AC: 2886 AN: 10592

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

European-Non Finnish (NFE) AF: 0.336 AC: 22877 AN: 67992

Other (OTH) AF: 0.334 AC: 703 AN: 2104

Alfa AF: 0.325 Hom.: 1006

Bravo AF: 0.328

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	-0.77
CADD	Benign	15
DANN	Benign	0.79
PhyloP100		2.1
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: rs7978610; hg19: chr12-124468572;