rs6060717

Variant names:

• chr20-35956725-T-C
• rs6060717
• ENST00000373991.3:c.-818-1623A>G

Variant summary

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

The ENST00000373991.3(SCAND1):​c.-818-1623A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,084 control chromosomes in the GnomAD database, including 6,193 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 0.26 (6193 hom., cov: 32)
• Consequence: SCAND1 ENST00000373991.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.297
• Publications: 13 publications found

Genes affected

SCAND1 (HGNC:10566): (SCAN domain containing 1) This gene encodes a SCAN box domain-containing protein. The SCAN domain is a highly conserved, leucine-rich motif of approximately 60 aa originally found within a subfamily of zinc finger proteins. This gene belongs to a family of genes that encode an isolated SCAN domain, but no zinc finger motif. This protein binds to and may regulate the function of the transcription factor myeloid zinc finger 1B. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Jan 2011]

CNBD2 (HGNC:16145): (cyclic nucleotide binding domain containing 2) Predicted to enable cAMP binding activity. Predicted to be involved in spermatogenesis. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCAND1	NM_001385710.1	c.-818-1623A>G		intron_variant	Intron 2 of 2		NP_001372639.1
CNBD2	XM_047439921.1	c.175-996T>C		intron_variant	Intron 1 of 12		XP_047295877.1
CNBD2	XM_047439922.1	c.175-996T>C		intron_variant	Intron 1 of 12		XP_047295878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCAND1	ENST00000373991.3	c.-818-1623A>G		intron_variant	Intron 2 of 2	1		ENSP00000363103.3
CNBD2	ENST00000622112.4	c.175-996T>C		intron_variant	Intron 1 of 4	3		ENSP00000479333.1

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39519 AN: 151966 Hom.: 6146 Cov.: 32

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.260 AC: 39614 AN: 152084 Hom.: 6193 Cov.: 32 AF XY: 0.261 AC XY: 19396 AN XY: 74356

African (AFR) AF: 0.445 AC: 18437 AN: 41460

American (AMR) AF: 0.202 AC: 3085 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 723 AN: 3470

East Asian (EAS) AF: 0.174 AC: 899 AN: 5162

South Asian (SAS) AF: 0.366 AC: 1764 AN: 4820

European-Finnish (FIN) AF: 0.169 AC: 1794 AN: 10588

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12159 AN: 67998

Other (OTH) AF: 0.257 AC: 543 AN: 2112

Alfa AF: 0.211 Hom.: 2035

Bravo AF: 0.262

Asia WGS AF: 0.349 AC: 1207 AN: 3450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.4
DANN	Benign	0.75
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6060717; hg19: chr20-34544647;