rs503677

Variant names:

• chr10-68067255-G-A
• rs503677
• NM_015601.4:c.226+5628C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-68067255-G-A
• chr10-68067255-G-C
• chr10-68067255-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_015601.4(HERC4):​c.226+5628C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 152,478 control chromosomes in the GnomAD database, including 25,564 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 0.53 (25531 hom., cov: 32)
  • Exomes 𝑓: 0.41 (33 hom.)
• Consequence: HERC4 NM_015601.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.32
• Publications: 4 publications found

Genes affected

HERC4 (HGNC:24521): (HECT and RLD domain containing E3 ubiquitin protein ligase 4) HERC4 belongs to the HERC family of ubiquitin ligases, all of which contain a HECT domain and at least 1 RCC1 (MIM 179710)-like domain (RLD). The 350-amino acid HECT domain is predicted to catalyze the formation of a thioester with ubiquitin before transferring it to a substrate, and the RLD is predicted to act as a guanine nucleotide exchange factor for small G proteins (Hochrainer et al., 2005 [PubMed 15676274]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.854 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015601.4. 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
	HERC4	NM_015601.4	MANE Select	c.226+5628C>T		intron	N/A	NP_056416.2
	HERC4	NM_022079.3		c.226+5628C>T		intron	N/A	NP_071362.1	Q5GLZ8-1
	HERC4	NM_001278185.2		c.226+5628C>T		intron	N/A	NP_001265114.1	Q5GLZ8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HERC4	ENST00000373700.9	TSL:1 MANE Select	c.226+5628C>T		intron	N/A	ENSP00000362804.4	Q5GLZ8-2
	HERC4	ENST00000395198.7	TSL:1	c.226+5628C>T		intron	N/A	ENSP00000378624.3	Q5GLZ8-1
	HERC4	ENST00000412272.6	TSL:1	c.226+5628C>T		intron	N/A	ENSP00000416504.2	Q5GLZ8-3

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80766 AN: 151928 Hom.: 25465 Cov.: 32

Gnomad AFR AF: 0.862

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.848

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.496

GnomAD4 exome AF: 0.410 AC: 177 AN: 432 Hom.: 33 Cov.: 0 AF XY: 0.400 AC XY: 104 AN XY: 260

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.411 AC: 175 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.532 AC: 80895 AN: 152046 Hom.: 25531 Cov.: 32 AF XY: 0.536 AC XY: 39832 AN XY: 74330

African (AFR) AF: 0.862 AC: 35791 AN: 41522

American (AMR) AF: 0.497 AC: 7587 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1143 AN: 3464

East Asian (EAS) AF: 0.849 AC: 4397 AN: 5182

South Asian (SAS) AF: 0.560 AC: 2697 AN: 4814

European-Finnish (FIN) AF: 0.420 AC: 4428 AN: 10550

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.342 AC: 23236 AN: 67942

Other (OTH) AF: 0.491 AC: 1032 AN: 2100

Alfa AF: 0.413 Hom.: 5311

Bravo AF: 0.556

Asia WGS AF: 0.654 AC: 2274 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	20
DANN	Benign	0.80
PhyloP100		2.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs503677; hg19: chr10-69827012;