rs4752928

Variant names:

• chr11-46701181-T-C
• rs4752928
• NM_024741.3:c.52+82T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-46701181-T-C
• chr11-46701181-T-A
• chr11-46701181-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024741.3(ZNF408):​c.52+82T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 1 in 1,609,898 control chromosomes in the GnomAD database, including 804,735 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 1.0 (76040 hom., cov: 30)
  • Exomes 𝑓: 1.0 (728695 hom.)
• Consequence: ZNF408 NM_024741.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.497
• Publications: 6 publications found

Genes affected

ZNF408 (HGNC:20041): (zinc finger protein 408) The protein encoded by this gene contains ten tandem zinc fingers and an N-terminal SET domain, so it is likely a DNA binding protein that interacts with other proteins. In adults, the encoded protein is expressed most highly in retina. Consequently, defects in this gene have been associated with familial exudative vitreoretinopathy (FEVR) and retinitis pigmentosa (RP). [provided by RefSeq, Dec 2016]

ARHGAP1 (HGNC:673): (Rho GTPase activating protein 1) This gene encodes a member of a large family of proteins that activate Rho-type guanosine triphosphate (GTP) metabolizing enzymes. The encoded protein contains a SRC homology 3 domain and interacts with Bcl-2-associated protein family members. [provided by RefSeq, Aug 2012]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-46701181-T-C is Benign according to our data. Variant chr11-46701181-T-C is described in ClinVar as Benign. ClinVar VariationId is 1274687.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024741.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF408	NM_024741.3	MANE Select	c.52+82T>C		intron	N/A	NP_079017.1	Q9H9D4
	ZNF408	NM_001184751.2		c.28+40T>C		intron	N/A	NP_001171680.1	B4DXY4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF408	ENST00000311764.3	TSL:1 MANE Select	c.52+82T>C		intron	N/A	ENSP00000309606.2	Q9H9D4
	ZNF408	ENST00000877975.1		c.52+82T>C		intron	N/A	ENSP00000548034.1
	ZNF408	ENST00000526410.1	TSL:3	n.69+82T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.999 AC: 152060 AN: 152158 Hom.: 75981 Cov.: 30

Gnomad AFR AF: 0.998

Gnomad AMI AF: 1.00

Gnomad AMR AF: 1.00

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 1.00

GnomAD2 exomes AF: 1.00 AC: 244914 AN: 244966 AF XY: 1.00

Gnomad AFR exome AF: 0.997

Gnomad AMR exome AF: 1.00

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 1.00

GnomAD4 exome AF: 1.00 AC: 1457506 AN: 1457622 Hom.: 728695 Cov.: 32 AF XY: 1.00 AC XY: 725263 AN XY: 725308

African (AFR) AF: 0.997 AC: 33314 AN: 33418

American (AMR) AF: 1.00 AC: 44611 AN: 44616

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 26104 AN: 26104

East Asian (EAS) AF: 1.00 AC: 39676 AN: 39678

South Asian (SAS) AF: 1.00 AC: 86188 AN: 86188

European-Finnish (FIN) AF: 1.00 AC: 52342 AN: 52342

Middle Eastern (MID) AF: 1.00 AC: 5748 AN: 5748

European-Non Finnish (NFE) AF: 1.00 AC: 1109265 AN: 1109268

Other (OTH) AF: 1.00 AC: 60258 AN: 60260

GnomAD4 genome AF: 0.999 AC: 152178 AN: 152276 Hom.: 76040 Cov.: 30 AF XY: 0.999 AC XY: 74412 AN XY: 74454

African (AFR) AF: 0.998 AC: 41462 AN: 41556

American (AMR) AF: 1.00 AC: 15289 AN: 15290

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5166 AN: 5166

South Asian (SAS) AF: 1.00 AC: 4825 AN: 4826

European-Finnish (FIN) AF: 1.00 AC: 10618 AN: 10618

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68027 AN: 68028

Other (OTH) AF: 1.00 AC: 2113 AN: 2114

Alfa AF: 1.00 Hom.: 14471

Bravo AF: 0.999

Asia WGS AF: 1.00 AC: 3478 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.6
DANN	Benign	0.56
PhyloP100		-0.50
PromoterAI		0.026	Neutral
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: rs4752928; hg19: chr11-46722731;