rs2448020

Positions:

• chr1-90918032-T-G

Variant summary

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

The NM_201269.3(ZNF644):​c.3791+20A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 1,587,532 control chromosomes in the GnomAD database, including 13,560 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 0.11 (1055 hom., cov: 32)
  • Exomes 𝑓: 0.13 (12505 hom.)
• Consequence: ZNF644 NM_201269.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75

Genes affected

ZNF644 (HGNC:29222): (zinc finger protein 644) The protein encoded by this gene is a zinc finger transcription factor that may play a role in eye development. Defects in this gene have been associated with high myopia. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF644	NM_201269.3	c.3791+20A>C		intron_variant		ENST00000337393.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF644	ENST00000337393.10	c.3791+20A>C		intron_variant		1	NM_201269.3	P1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17382 AN: 152110 Hom.: 1058 Cov.: 32

Gnomad AFR AF: 0.0812

Gnomad AMI AF: 0.0637

Gnomad AMR AF: 0.0774

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.117

GnomAD3 exomes AF: 0.121 AC: 30327 AN: 251074 Hom.: 2022 AF XY: 0.124 AC XY: 16859 AN XY: 135682

Gnomad AFR exome AF: 0.0758

Gnomad AMR exome AF: 0.0533

Gnomad ASJ exome AF: 0.194

Gnomad EAS exome AF: 0.169

Gnomad SAS exome AF: 0.151

Gnomad FIN exome AF: 0.111

Gnomad NFE exome AF: 0.127

Gnomad OTH exome AF: 0.120

GnomAD4 exome AF: 0.129 AC: 185096 AN: 1435306 Hom.: 12505 Cov.: 25 AF XY: 0.130 AC XY: 93043 AN XY: 715742

Gnomad4 AFR exome AF: 0.0758

Gnomad4 AMR exome AF: 0.0572

Gnomad4 ASJ exome AF: 0.196

Gnomad4 EAS exome AF: 0.116

Gnomad4 SAS exome AF: 0.154

Gnomad4 FIN exome AF: 0.112

Gnomad4 NFE exome AF: 0.131

Gnomad4 OTH exome AF: 0.136

GnomAD4 genome AF: 0.114 AC: 17384 AN: 152226 Hom.: 1055 Cov.: 32 AF XY: 0.113 AC XY: 8430 AN XY: 74434

Gnomad4 AFR AF: 0.0813

Gnomad4 AMR AF: 0.0773

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.116

Alfa AF: 0.127 Hom.: 1298

Bravo AF: 0.109

Asia WGS AF: 0.115 AC: 398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.021
DANN	Benign	0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2448020; hg19: chr1-91383589; COSMIC: COSV61346547;