rs10111051

Variant names:

• chr8-10695962-A-G
• rs10111051
• NM_001040032.2:c.242-1637A>G

Variant summary

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

The NM_001040032.2(C8orf74):​c.242-1637A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,146 control chromosomes in the GnomAD database, including 5,984 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 0.17 (5984 hom., cov: 32)
• Consequence: C8orf74 NM_001040032.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.496
• Publications: 0 publications found

Genes affected

C8orf74 (HGNC:32296): (chromosome 8 open reading frame 74)

RP1L1 (HGNC:15946): (RP1 like 1) This gene encodes a member of the doublecortin family. The protein encoded by this gene contains two N-terminal doublecortin domains, which bind microtubules and regulate microtubule polymerization, and two C-terminal large repetitive regions, both of which contain a high percentage of glutamine and glutamic acid residues. This protein is a retinal-specific protein. Its exact length varies among individuals due to the presence of a 16aa repeat in the first C-terminal repetitive region. The 16aa repeat is encoded by the highly polymorphic 48-bp repeat, and 1-6 copies of the 16aa repeat have been identified in normal individuals. The current reference sequence shown here has a single copy of the 16aa repeat. This protein and the RP1 protein, another retinal-specific protein, play essential and synergistic roles in affecting photosensitivity and outer segment morphogenesis of rod photoreceptors. Mutations in this gene cause occult macular dystrophy (OMD). [provided by RefSeq, Sep 2010]

RP1L1 Gene-Disease associations (from GenCC):

• occult macular dystrophy

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Laboratory for Molecular Medicine
• retinitis pigmentosa

  Inheritance: AD, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
• retinitis pigmentosa 88

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• cone dystrophy

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C8orf74	NM_001040032.2	c.242-1637A>G		intron_variant	Intron 2 of 3	ENST00000304519.10	NP_001035121.2
C8orf74	XM_047421493.1	c.299-1637A>G		intron_variant	Intron 2 of 3		XP_047277449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C8orf74	ENST00000304519.10	c.242-1637A>G		intron_variant	Intron 2 of 3	1	NM_001040032.2	ENSP00000307129.5
RP1L1	ENST00000329335.3	n.231+15995T>C		intron_variant	Intron 1 of 2	2
C8orf74	ENST00000523289.5	n.*134-1637A>G		intron_variant	Intron 3 of 4	2		ENSP00000430613.1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25037 AN: 152028 Hom.: 5960 Cov.: 32

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.0439

Gnomad FIN AF: 0.0365

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00444

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.165 AC: 25114 AN: 152146 Hom.: 5984 Cov.: 32 AF XY: 0.163 AC XY: 12143 AN XY: 74398

African (AFR) AF: 0.525 AC: 21769 AN: 41448

American (AMR) AF: 0.105 AC: 1608 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00260 AC: 9 AN: 3468

East Asian (EAS) AF: 0.109 AC: 563 AN: 5164

South Asian (SAS) AF: 0.0445 AC: 215 AN: 4830

European-Finnish (FIN) AF: 0.0365 AC: 388 AN: 10620

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00444 AC: 302 AN: 68010

Other (OTH) AF: 0.117 AC: 248 AN: 2114

Alfa AF: 0.145 Hom.: 899

Bravo AF: 0.185

Asia WGS AF: 0.108 AC: 375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.94
DANN	Benign	0.39
PhyloP100		-0.50
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: rs10111051; hg19: chr8-10553472;