rs1187415

chr12-124006982-G-Cchr12-124006982-G-T

Variant summary

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

The NM_152437.3(ZNF664):c.-660-4399G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 152,000 control chromosomes in the GnomAD database, including 29,566 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 0.61 (29566 hom., cov: 31)
• Consequence: ZNF664 NM_152437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.264

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF664	NM_152437.3	c.-660-4399G>C		intron_variant		ENST00000337815.9
ZNF664-RFLNA	NM_001204299.3	c.-234+32962G>C		intron_variant
ZNF664	NM_001204298.2	c.-660-4399G>C		intron_variant
ZNF664-RFLNA	NM_001347902.2	c.-234+32962G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF664	ENST00000337815.9	c.-660-4399G>C		intron_variant		1	NM_152437.3	P1

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92839 AN: 151882 Hom.: 29560 Cov.: 31

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.907

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.719

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.601

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

GnomAD4 genome AF: 0.611 AC: 92882 AN: 152000 Hom.: 29566 Cov.: 31 AF XY: 0.621 AC XY: 46129 AN XY: 74290

Gnomad4 AFR AF: 0.431

Gnomad4 AMR AF: 0.672

Gnomad4 ASJ AF: 0.564

Gnomad4 EAS AF: 0.907

Gnomad4 SAS AF: 0.784

Gnomad4 FIN AF: 0.719

Gnomad4 NFE AF: 0.659

Gnomad4 OTH AF: 0.604

Alfa AF: 0.628 Hom.: 3654

Bravo AF: 0.595

Asia WGS AF: 0.768 AC: 2672 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.49
Dann	Benign	0.50

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: rs1187415; hg19: chr12-124491529;