6-49848219-C-T

Variant names:

• chr6-49848219-C-T
• rs143712708
• NM_001131.3:c.276G>A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001131.3(CRISP1):​c.276G>A​(p.Arg92Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00193 in 1,584,602 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0020 (5 hom.)
• Consequence: CRISP1 NM_001131.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.259

Genes affected

CRISP1 (HGNC:304): (cysteine rich secretory protein 1) Fertilization consists of a sequence of specific cell-cell interactions culminating in the fusion of the sperm and egg plasma membranes. Recognition, binding, and fusion occur through the interaction of complementary molecules that are localized to specific domains of the sperm and egg plasma membranes. In the sperm, the postacrosomal region or equatorial segment is involved in sperm-egg plasma membrane fusion. The protein encoded by this gene is a member of the cysteine-rich secretory protein (CRISP) family. It is expressed in the epididymis, is secreted into the epididymal lumen, and binds to the postacrosomal region of the sperm head, where it plays a role in sperm-egg fusion. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 6-49848219-C-T is Benign according to our data. Variant chr6-49848219-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2656638.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.259 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRISP1	NM_001131.3	c.276G>A	p.Arg92Arg	synonymous_variant	Exon 4 of 8	ENST00000335847.9	NP_001122.2
CRISP1	NM_001205220.2	c.276G>A	p.Arg92Arg	synonymous_variant	Exon 4 of 8		NP_001192149.1
CRISP1	NM_170609.2	c.276G>A	p.Arg92Arg	synonymous_variant	Exon 4 of 7		NP_733758.1
CRISP1	XM_017010320.3	c.-506G>A		upstream_gene_variant			XP_016865809.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRISP1	ENST00000335847.9	c.276G>A	p.Arg92Arg	synonymous_variant	Exon 4 of 8	1	NM_001131.3	ENSP00000338276.4
CRISP1	ENST00000505118.1	c.276G>A	p.Arg92Arg	synonymous_variant	Exon 4 of 8	1		ENSP00000427589.1
CRISP1	ENST00000507853.5	c.276G>A	p.Arg92Arg	synonymous_variant	Exon 4 of 7	1		ENSP00000425020.1
CRISP1	ENST00000329411.9	c.276G>A	p.Arg92Arg	synonymous_variant	Exon 3 of 6	5		ENSP00000331317.5

Frequencies

GnomAD3 genomes AF: 0.00109 AC: 163 AN: 150216 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000635

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000133

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00112

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00182

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00108 AC: 251 AN: 232270 Hom.: 0 AF XY: 0.00111 AC XY: 140 AN XY: 125922

Gnomad AFR exome AF: 0.000193

Gnomad AMR exome AF: 0.000100

Gnomad ASJ exome AF: 0.000752

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000960

Gnomad NFE exome AF: 0.00197

Gnomad OTH exome AF: 0.000896

GnomAD4 exome AF: 0.00202 AC: 2899 AN: 1434274 Hom.: 5 Cov.: 30 AF XY: 0.00196 AC XY: 1399 AN XY: 713496

Gnomad4 AFR exome AF: 0.000345

Gnomad4 AMR exome AF: 0.000125

Gnomad4 ASJ exome AF: 0.000595

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000863

Gnomad4 NFE exome AF: 0.00252

Gnomad4 OTH exome AF: 0.000795

GnomAD4 genome AF: 0.00108 AC: 163 AN: 150328 Hom.: 1 Cov.: 31 AF XY: 0.000983 AC XY: 72 AN XY: 73208

Gnomad4 AFR AF: 0.000633

Gnomad4 AMR AF: 0.000133

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00112

Gnomad4 NFE AF: 0.00182

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00171 Hom.: 1

Bravo AF: 0.00108

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CRISP1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.8
DANN	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs143712708; hg19: chr6-49815932;