Genetic Variant NM_003040.4:c.-63-194C>T (chr7-151061731-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_003040.4(SLC4A2):c.-63-194C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000265 in 490,242 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

SLC4A2
NM_003040.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.43

Publications

3 publications found

Variant links:

Genes affected

SLC4A2 (HGNC:11028): (solute carrier family 4 member 2) This gene encodes a member of the anion exchanger family of membrane transport proteins. The encoded protein regulates intracellular pH, biliary bicarbonate secretion, and chloride uptake. Reduced expression of this gene may be associated with primary biliary cirrhosis (PBC) in human patients, while differential expression of this gene may be associated with malignant hepatocellular carcinoma, colon and gastric cancers. [provided by RefSeq, Nov 2016]

SLC4A2 Gene-Disease associations (from GenCC):

hereditary spherocytosis type 4
Inheritance: AD Classification: MODERATE Submitted by: G2P
osteopetrosis, autosomal recessive 9
Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia

SLC4A2 links:

LOC128092247 (HGNC:0):

LOC128092247 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003040.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC4A2	NM_003040.4	MANE Select	c.-63-194C>T	intron	N/A	NP_003031.3
SLC4A2	NM_001199692.3		c.-63-194C>T	intron	N/A	NP_001186621.1	P04920-1
LOC128092247	NM_001414898.1	MANE Select	c.-197C>T	upstream_gene	N/A	NP_001401827.1	A0A6Q8PFQ6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC4A2	ENST00000413384.7	TSL:1 MANE Select	c.-63-194C>T	intron	N/A	ENSP00000405600.2	P04920-1
SLC4A2	ENST00000485713.6	TSL:1	c.-63-194C>T	intron	N/A	ENSP00000419412.1
SLC4A2	ENST00000488420.1	TSL:3	c.-257C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	ENSP00000417221.1	C9J459

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152116

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:

0.000388

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000325

AC:

AN:

338126

Hom.:

Cov.:

AF XY:

0.0000342

AC XY:

AN XY:

175382

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

11120

American (AMR)

AF:

0.00

AC:

AN:

15352

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11138

East Asian (EAS)

AF:

0.000318

AC:

AN:

28300

South Asian (SAS)

AF:

0.00

AC:

AN:

23320

European-Finnish (FIN)

AF:

0.0000871

AC:

AN:

22970

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1608

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

203940

Other (OTH)

AF:

0.00

AC:

AN:

20378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

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:

0.0000131

AC:

AN:

152116

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41430

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000388

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68006

Other (OTH)

AF:

0.00

AC:

AN:

2094

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

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.29

(source)

DANN

Benign

0.71

PhyloP100

-3.4

PromoterAI

-0.025

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

0.95

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over