rs61407177

Variant names:

• chr19-7645187-C-T
• rs61407177
• NM_006949.4:c.1247-10C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-7645187-C-T
• chr19-7645187-C-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006949.4(STXBP2):​c.1247-10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0129 in 1,555,264 control chromosomes in the GnomAD database, including 939 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.039 (262 hom., cov: 34)
  • Exomes 𝑓: 0.010 (677 hom.)
• Consequence: STXBP2 NM_006949.4 intron
• Scores: Splicing: ADA: 0.00001560
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.77
• Publications: 2 publications found

Genes affected

STXBP2 (HGNC:11445): (syntaxin binding protein 2) This gene encodes a member of the STXBP/unc-18/SEC1 family. The encoded protein is involved in intracellular trafficking, control of SNARE (soluble NSF attachment protein receptor) complex assembly, and the release of cytotoxic granules by natural killer cells. Mutations in this gene are associated with familial hemophagocytic lymphohistiocytosis. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jan 2013]

STXBP2 Gene-Disease associations (from GenCC):

• familial hemophagocytic lymphohistiocytosis 5

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• hereditary hemophagocytic lymphohistiocytosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• microvillus inclusion disease

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000268400 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 19-7645187-C-T is Benign according to our data. Variant chr19-7645187-C-T is described in ClinVar as Benign. ClinVar VariationId is 260086.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006949.4. 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
	STXBP2	NM_006949.4	MANE Select	c.1247-10C>T		intron	N/A	NP_008880.2	Q15833-1
	STXBP2	NM_001272034.2		c.1280-10C>T		intron	N/A	NP_001258963.1	Q15833-3
	STXBP2	NM_001127396.3		c.1238-10C>T		intron	N/A	NP_001120868.1	Q15833-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STXBP2	ENST00000221283.10	TSL:1 MANE Select	c.1247-10C>T		intron	N/A	ENSP00000221283.4	Q15833-1
	STXBP2	ENST00000414284.6	TSL:1	c.1238-10C>T		intron	N/A	ENSP00000409471.1	Q15833-2
	STXBP2	ENST00000597068.5	TSL:1	n.1222-10C>T		intron	N/A	ENSP00000471327.1	M0R0M7

Frequencies

GnomAD3 genomes AF: 0.0392 AC: 5968 AN: 152196 Hom.: 257 Cov.: 34

Gnomad AFR AF: 0.0756

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.0300

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.0471

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00215

Gnomad OTH AF: 0.0377

GnomAD2 exomes AF: 0.0394 AC: 6406 AN: 162392 AF XY: 0.0321

Gnomad AFR exome AF: 0.0804

Gnomad AMR exome AF: 0.164

Gnomad ASJ exome AF: 0.0278

Gnomad EAS exome AF: 0.0288

Gnomad FIN exome AF: 0.0402

Gnomad NFE exome AF: 0.00193

Gnomad OTH exome AF: 0.0320

GnomAD4 exome AF: 0.00998 AC: 14000 AN: 1402950 Hom.: 677 Cov.: 33 AF XY: 0.00910 AC XY: 6299 AN XY: 692406

African (AFR) AF: 0.0791 AC: 2516 AN: 31818

American (AMR) AF: 0.158 AC: 5732 AN: 36252

Ashkenazi Jewish (ASJ) AF: 0.0278 AC: 702 AN: 25238

East Asian (EAS) AF: 0.0271 AC: 981 AN: 36144

South Asian (SAS) AF: 0.00171 AC: 136 AN: 79600

European-Finnish (FIN) AF: 0.0382 AC: 1886 AN: 49426

Middle Eastern (MID) AF: 0.00789 AC: 45 AN: 5702

European-Non Finnish (NFE) AF: 0.000857 AC: 926 AN: 1080608

Other (OTH) AF: 0.0185 AC: 1076 AN: 58162

GnomAD4 genome AF: 0.0393 AC: 5992 AN: 152314 Hom.: 262 Cov.: 34 AF XY: 0.0416 AC XY: 3102 AN XY: 74484

African (AFR) AF: 0.0759 AC: 3155 AN: 41560

American (AMR) AF: 0.120 AC: 1833 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0285 AC: 99 AN: 3472

East Asian (EAS) AF: 0.0297 AC: 154 AN: 5180

South Asian (SAS) AF: 0.00352 AC: 17 AN: 4832

European-Finnish (FIN) AF: 0.0471 AC: 500 AN: 10626

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00215 AC: 146 AN: 68022

Other (OTH) AF: 0.0373 AC: 79 AN: 2116

Alfa AF: 0.0236 Hom.: 38

Bravo AF: 0.0466

Asia WGS AF: 0.0360 AC: 123 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	Familial hemophagocytic lymphohistiocytosis 5 (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.93
DANN	Benign	0.45
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000016
dbscSNV1_RF	Benign	0.0
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: rs61407177; hg19: chr19-7710073;