Genetic Variant NM_057176.3:c.-70C>G (chr1-54999117-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_057176.3(BSND):c.-70C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 1,581,328 control chromosomes in the GnomAD database, including 439,563 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.67 ( 35246 hom., cov: 33)

Exomes 𝑓: 0.75 ( 404317 hom. )

Consequence

BSND
NM_057176.3 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.06

Publications

16 publications found

Variant links:

Genes affected

BSND (HGNC:16512): (barttin CLCNK type accessory subunit beta) This gene encodes an essential beta subunit for CLC chloride channels. These heteromeric channels localize to basolateral membranes of renal tubules and of potassium-secreting epithelia of the inner ear. Mutations in this gene have been associated with Bartter syndrome with sensorineural deafness. [provided by RefSeq, Jul 2008]

BSND Gene-Disease associations (from GenCC):

Bartter disease type 4A
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P
Bartter syndrome type 4
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

BSND links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 1-54999117-C-G is Benign according to our data. Variant chr1-54999117-C-G is described in ClinVar as Benign. ClinVar VariationId is 297674.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_057176.3. 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
	BSND	NM_057176.3	MANE Select	c.-70C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	NP_476517.1	Q8WZ55
	BSND	NM_057176.3	MANE Select	c.-70C>G		5_prime_UTR	Exon 1 of 4	NP_476517.1	Q8WZ55

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BSND	ENST00000651561.1	MANE Select	c.-70C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	ENSP00000498282.1	Q8WZ55
	BSND	ENST00000651561.1	MANE Select	c.-70C>G		5_prime_UTR	Exon 1 of 4	ENSP00000498282.1	Q8WZ55

Frequencies

GnomAD3 genomes

AF:

0.670

AC:

101800

AN:

151972

Hom.:

35240

Cov.:

show subpopulations

Gnomad AFR

AF:

0.523

Gnomad AMI

AF:

0.759

Gnomad AMR

AF:

0.688

Gnomad ASJ

AF:

0.701

Gnomad EAS

AF:

0.336

Gnomad SAS

AF:

0.700

Gnomad FIN

AF:

0.651

Gnomad MID

AF:

0.677

Gnomad NFE

AF:

0.779

Gnomad OTH

AF:

0.670

GnomAD4 exome

AF:

0.747

AC:

1067966

AN:

1429238

Hom.:

404317

Cov.:

AF XY:

0.747

AC XY:

532516

AN XY:

712486

show subpopulations

African (AFR)

AF:

0.509

AC:

16694

AN:

32824

American (AMR)

AF:

0.654

AC:

29101

AN:

44508

Ashkenazi Jewish (ASJ)

AF:

0.698

AC:

18057

AN:

25852

East Asian (EAS)

AF:

0.384

AC:

15155

AN:

39468

South Asian (SAS)

AF:

0.708

AC:

60687

AN:

85662

European-Finnish (FIN)

AF:

0.676

AC:

31382

AN:

46442

Middle Eastern (MID)

AF:

0.694

AC:

3968

AN:

5714

European-Non Finnish (NFE)

AF:

0.781

AC:

850325

AN:

1089340

Other (OTH)

AF:

0.717

AC:

42597

AN:

59428

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

13358

26715

40073

53430

66788

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19888

39776

59664

79552

99440

<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:

0.670

AC:

101853

AN:

152090

Hom.:

35246

Cov.:

AF XY:

0.662

AC XY:

49238

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.523

AC:

21684

AN:

41480

American (AMR)

AF:

0.688

AC:

10509

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.701

AC:

2432

AN:

3470

East Asian (EAS)

AF:

0.336

AC:

1727

AN:

5142

South Asian (SAS)

AF:

0.700

AC:

3378

AN:

4826

European-Finnish (FIN)

AF:

0.651

AC:

6895

AN:

10584

Middle Eastern (MID)

AF:

0.656

AC:

193

AN:

294

European-Non Finnish (NFE)

AF:

0.779

AC:

52935

AN:

67992

Other (OTH)

AF:

0.668

AC:

1409

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.529

Heterozygous variant carriers

1668

3337

5005

6674

8342

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

806

1612

2418

3224

4030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.662

Hom.:

2312

Bravo

AF:

0.660

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Bartter disease type 4A (2)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.3

(source)

DANN

Benign

0.64

PhyloP100

-1.1

PromoterAI

-0.026

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over