6-49697191-G-T

Variant names:

• chr6-49697191-G-T
• rs360555
• NM_003296.4:c.515+669C>A

Variant summary

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

The NM_003296.4(CRISP2):​c.515+669C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,026 control chromosomes in the GnomAD database, including 1,573 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 0.14 (1573 hom., cov: 33)
• Consequence: CRISP2 NM_003296.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.885
• Publications: 3 publications found

Genes affected

CRISP2 (HGNC:12024): (cysteine rich secretory protein 2) Predicted to be involved in cell-cell adhesion. Predicted to be active in extracellular space. [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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRISP2	NM_003296.4	c.515+669C>A		intron_variant	Intron 8 of 9	ENST00000339139.5	NP_003287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRISP2	ENST00000339139.5	c.515+669C>A		intron_variant	Intron 8 of 9	1	NM_003296.4	ENSP00000339155.4
CRISP2	ENST00000618917.4	c.620+485C>A		intron_variant	Intron 9 of 10	5		ENSP00000482890.1
CRISP2	ENST00000616725.4	c.515+669C>A		intron_variant	Intron 7 of 8	5		ENSP00000484609.1

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20757 AN: 151908 Hom.: 1572 Cov.: 33

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.0855

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.137 AC: 20778 AN: 152026 Hom.: 1573 Cov.: 33 AF XY: 0.136 AC XY: 10097 AN XY: 74324

African (AFR) AF: 0.196 AC: 8103 AN: 41444

American (AMR) AF: 0.0853 AC: 1301 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 406 AN: 3466

East Asian (EAS) AF: 0.170 AC: 881 AN: 5176

South Asian (SAS) AF: 0.128 AC: 617 AN: 4810

European-Finnish (FIN) AF: 0.130 AC: 1378 AN: 10572

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7724 AN: 67984

Other (OTH) AF: 0.130 AC: 275 AN: 2114

Alfa AF: 0.0875 Hom.: 141

Bravo AF: 0.135

Asia WGS AF: 0.148 AC: 518 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.30
DANN	Benign	0.31
PhyloP100		-0.89
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: rs360555; hg19: chr6-49664904;