Genetic Variant NM_032108.4:c.2527C>T (chr19-4543741-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_032108.4(SEMA6B):c.2527C>T(p.Leu843Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000204 in 1,227,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

SEMA6B
NM_032108.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.588

Publications

0 publications found

Variant links:

Genes affected

SEMA6B (HGNC:10739): (semaphorin 6B) This gene encodes a member of the semaphorin family, a group of proteins characterized by the presence of a conserved semaphorin (sema) domain. Whereas some semaphorins are transmembrane proteins, others are secreted. Semaphorins play a major role in axon guidance. The protein encoded by this gene may be involved in both peripheral and central nervous system development. [provided by RefSeq, Jul 2008]

SEMA6B Gene-Disease associations (from GenCC):

progressive myoclonus epilepsy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
epilepsy, progressive myoclonic, 11
Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
intellectual disability
Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia

SEMA6B links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 19-4543741-G-A is Benign according to our data. Variant chr19-4543741-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2649066.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.588 with no splicing effect.

BS2

High AC in GnomAdExome4 at 24 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032108.4. 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
	SEMA6B	NM_032108.4	MANE Select	c.2527C>T	p.Leu843Leu	synonymous	Exon 17 of 17	NP_115484.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEMA6B	ENST00000586582.6	TSL:1 MANE Select	c.2527C>T	p.Leu843Leu	synonymous	Exon 17 of 17	ENSP00000467290.1	Q9H3T3-1
SEMA6B	ENST00000586965.1	TSL:1	c.1852-645C>T		intron	N/A	ENSP00000465722.1	Q9H3T3-3
SEMA6B	ENST00000676793.2		c.2527C>T	p.Leu843Leu	synonymous	Exon 17 of 17	ENSP00000503414.1	Q9H3T3-1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000223

AC:

AN:

1075434

Hom.:

Cov.:

AF XY:

0.0000158

AC XY:

AN XY:

507814

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22708

American (AMR)

AF:

0.00

AC:

AN:

8272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14134

East Asian (EAS)

AF:

0.00

AC:

AN:

26232

South Asian (SAS)

AF:

0.00

AC:

AN:

19462

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21070

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2898

European-Non Finnish (NFE)

AF:

0.0000251

AC:

AN:

917306

Other (OTH)

AF:

0.0000231

AC:

AN:

43352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152058

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41440

American (AMR)

AF:

0.00

AC:

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10568

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67986

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

8.5

(source)

DANN

Benign

0.90

PhyloP100

0.59

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over