chr8-61458701-C-T

Variant names:

• chr8-61458701-C-T
• rs2291607
• NM_173519.3:c.977+159C>T

Variant summary

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

The NM_173519.3(CLVS1):​c.977+159C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 575,490 control chromosomes in the GnomAD database, including 162,004 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 0.63 (34472 hom., cov: 32)
  • Exomes 𝑓: 0.77 (127532 hom.)
• Consequence: CLVS1 NM_173519.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.192
• Publications: 3 publications found

Genes affected

CLVS1 (HGNC:23139): (clavesin 1) Enables phosphatidylinositol-3,5-bisphosphate binding activity. Predicted to be involved in lysosome organization. Located in endosome. [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=-0.47).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLVS1	NM_173519.3	c.977+159C>T		intron_variant	Intron 5 of 5	ENST00000325897.5	NP_775790.1
CLVS1	XM_017013141.2	c.977+159C>T		intron_variant	Intron 6 of 6		XP_016868630.1
CLVS1	XM_017013142.3	c.977+159C>T		intron_variant	Intron 6 of 6		XP_016868631.1
CLVS1	XM_024447079.2	c.977+159C>T		intron_variant	Intron 8 of 8		XP_024302847.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLVS1	ENST00000325897.5	c.977+159C>T		intron_variant	Intron 5 of 5	1	NM_173519.3	ENSP00000325506.4

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95878 AN: 151922 Hom.: 34464 Cov.: 32

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.709

Gnomad ASJ AF: 0.768

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.745

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.794

Gnomad OTH AF: 0.657

GnomAD4 exome AF: 0.769 AC: 325763 AN: 423450 Hom.: 127532 Cov.: 5 AF XY: 0.772 AC XY: 170599 AN XY: 220898

African (AFR) AF: 0.252 AC: 2985 AN: 11856

American (AMR) AF: 0.726 AC: 9392 AN: 12940

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 10089 AN: 12932

East Asian (EAS) AF: 0.790 AC: 22812 AN: 28894

South Asian (SAS) AF: 0.767 AC: 27069 AN: 35300

European-Finnish (FIN) AF: 0.759 AC: 23226 AN: 30592

Middle Eastern (MID) AF: 0.774 AC: 2351 AN: 3038

European-Non Finnish (NFE) AF: 0.796 AC: 209785 AN: 263512

Other (OTH) AF: 0.740 AC: 18054 AN: 24386

GnomAD4 genome AF: 0.631 AC: 95893 AN: 152040 Hom.: 34472 Cov.: 32 AF XY: 0.631 AC XY: 46850 AN XY: 74304

African (AFR) AF: 0.254 AC: 10543 AN: 41432

American (AMR) AF: 0.710 AC: 10845 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.768 AC: 2666 AN: 3470

East Asian (EAS) AF: 0.756 AC: 3915 AN: 5178

South Asian (SAS) AF: 0.766 AC: 3684 AN: 4808

European-Finnish (FIN) AF: 0.745 AC: 7862 AN: 10556

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.794 AC: 53990 AN: 67998

Other (OTH) AF: 0.657 AC: 1390 AN: 2116

Alfa AF: 0.743 Hom.: 132451

Bravo AF: 0.611

Asia WGS AF: 0.716 AC: 2493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	11
DANN	Benign	0.56
PhyloP100		0.19
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: rs2291607; hg19: chr8-62371260;