rs10152453

Variant names:

• chr15-63806414-C-A
• rs10152453
• NM_003922.4:c.-27+27413G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-63806414-C-A
• chr15-63806414-C-G

Variant summary

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

The NM_003922.4(HERC1):​c.-27+27413G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 152,060 control chromosomes in the GnomAD database, including 51,970 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 0.81 (51970 hom., cov: 31)
• Consequence: HERC1 NM_003922.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0260
• Publications: 3 publications found

Genes affected

HERC1 (HGNC:4867): (HECT and RLD domain containing E3 ubiquitin protein ligase family member 1) This gen encodes a member of the HERC protein family. This protein stimulates guanine nucleotide exchange on ARF1 and Rab proteins. This protein may be involved in membrane transport processes. [provided by RefSeq, Mar 2012]

HERC1 Gene-Disease associations (from GenCC):

• macrocephaly, dysmorphic facies, and psychomotor retardation

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• megalencephaly-severe kyphoscoliosis-overgrowth syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003922.4. 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
	HERC1	NM_003922.4	MANE Select	c.-27+27413G>T		intron	N/A	NP_003913.3	Q15751

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HERC1	ENST00000443617.7	TSL:1 MANE Select	c.-27+27413G>T		intron	N/A	ENSP00000390158.2	Q15751
	HERC1	ENST00000559886.1	TSL:1	n.91+27413G>T		intron	N/A
	HERC1	ENST00000561400.1	TSL:2	c.-27+27413G>T		intron	N/A	ENSP00000453937.1	H0YNB1

Frequencies

GnomAD3 genomes AF: 0.812 AC: 123334 AN: 151942 Hom.: 51915 Cov.: 31

Gnomad AFR AF: 0.851

Gnomad AMI AF: 0.887

Gnomad AMR AF: 0.722

Gnomad ASJ AF: 0.858

Gnomad EAS AF: 0.0914

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.825

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.872

Gnomad OTH AF: 0.803

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

GnomAD4 genome AF: 0.812 AC: 123447 AN: 152060 Hom.: 51970 Cov.: 31 AF XY: 0.800 AC XY: 59438 AN XY: 74316

African (AFR) AF: 0.851 AC: 35321 AN: 41492

American (AMR) AF: 0.721 AC: 11014 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.858 AC: 2978 AN: 3470

East Asian (EAS) AF: 0.0912 AC: 472 AN: 5174

South Asian (SAS) AF: 0.601 AC: 2891 AN: 4814

European-Finnish (FIN) AF: 0.825 AC: 8711 AN: 10560

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.872 AC: 59298 AN: 67966

Other (OTH) AF: 0.806 AC: 1698 AN: 2108

Alfa AF: 0.814 Hom.: 3285

Bravo AF: 0.801

Asia WGS AF: 0.398 AC: 1386 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.93
DANN	Benign	0.65
PhyloP100		-0.026
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: rs10152453; hg19: chr15-64098613;