1-243450446-G-A

Variant names:

• chr1-243450446-G-A
• rs11800122
• NM_006642.5:c.1985+23888G>A

Variant summary

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

The NM_001350248.2(SDCCAG8):​c.2081+23888G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,072 control chromosomes in the GnomAD database, including 2,850 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 0.19 (2850 hom., cov: 32)
• Consequence: SDCCAG8 NM_001350248.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202
• Publications: 6 publications found

Genes affected

SDCCAG8 (HGNC:10671): (SHH signaling and ciliogenesis regulator SDCCAG8) This gene encodes a centrosome associated protein. This protein may be involved in organizing the centrosome during interphase and mitosis. Mutations in this gene are associated with retinal-renal ciliopathy. [provided by RefSeq, Oct 2010]

SDCCAG8 Gene-Disease associations (from GenCC):

• Senior-Loken syndrome 7

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• Bardet-Biedl syndrome 16

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp
• Bardet-Biedl syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Senior-Loken 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 (AFR) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001350248.2. 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
	SDCCAG8	NM_006642.5	MANE Select	c.1985+23888G>A		intron	N/A	NP_006633.1
	SDCCAG8	NM_001350248.2		c.2081+23888G>A		intron	N/A	NP_001337177.1
	SDCCAG8	NM_001350249.2		c.1691+23888G>A		intron	N/A	NP_001337178.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDCCAG8	ENST00000366541.8	TSL:1 MANE Select	c.1985+23888G>A		intron	N/A	ENSP00000355499.3
	SDCCAG8	ENST00000435549.1	TSL:1	c.1088+23888G>A		intron	N/A	ENSP00000410200.1
	SDCCAG8	ENST00000884080.1		c.2081+23888G>A		intron	N/A	ENSP00000554139.1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28275 AN: 151952 Hom.: 2837 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.0930

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.186 AC: 28323 AN: 152072 Hom.: 2850 Cov.: 32 AF XY: 0.184 AC XY: 13702 AN XY: 74336

African (AFR) AF: 0.260 AC: 10763 AN: 41468

American (AMR) AF: 0.152 AC: 2319 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 394 AN: 3466

East Asian (EAS) AF: 0.0933 AC: 481 AN: 5158

South Asian (SAS) AF: 0.114 AC: 551 AN: 4814

European-Finnish (FIN) AF: 0.192 AC: 2031 AN: 10570

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11160 AN: 68004

Other (OTH) AF: 0.184 AC: 389 AN: 2112

Alfa AF: 0.170 Hom.: 6975

Bravo AF: 0.190

Asia WGS AF: 0.111 AC: 387 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	1.7
DANN	Benign	0.63
PhyloP100		0.20
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: rs11800122; hg19: chr1-243613748;