chr12-123990609-A-G

Position:

• chr12-123990609-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152437.3(ZNF664):​c.-661+2471A>G 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 152,096 control chromosomes in the GnomAD database, including 8,044 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 (8044 hom., cov: 32)
• Consequence: ZNF664 NM_152437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF664	NM_152437.3	c.-661+2471A>G		intron_variant		ENST00000337815.9	NP_689650.1
ZNF664-RFLNA	NM_001204299.3	c.-234+16589A>G		intron_variant			NP_001191228.1
ZNF664	NM_001204298.2	c.-661+2471A>G		intron_variant			NP_001191227.1
ZNF664-RFLNA	NM_001347902.2	c.-234+16589A>G		intron_variant			NP_001334831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF664	ENST00000337815.9	c.-661+2471A>G		intron_variant		1	NM_152437.3	ENSP00000337320	P1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48868 AN: 151978 Hom.: 8037 Cov.: 32

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.0938

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.339

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

GnomAD4 genome AF: 0.322 AC: 48911 AN: 152096 Hom.: 8044 Cov.: 32 AF XY: 0.314 AC XY: 23321 AN XY: 74342

Gnomad4 AFR AF: 0.351

Gnomad4 AMR AF: 0.296

Gnomad4 ASJ AF: 0.390

Gnomad4 EAS AF: 0.0936

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.271

Gnomad4 NFE AF: 0.337

Gnomad4 OTH AF: 0.336

Alfa AF: 0.327 Hom.: 3907

Bravo AF: 0.327

Asia WGS AF: 0.214 AC: 744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.26
DANN	Benign	0.39

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

Publications

LitVar

Other links and lift over

dbSNP: rs7307277; hg19: chr12-124475156;