chr16-71385579-T-C

Variant names:

• chr16-71385579-T-C
• rs2042560909
• NM_001740.5:c.630T>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4 BP6_Moderate

The NM_007088.4(CALB2):​c.536T>C​(p.Ile179Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: CALB2 NM_007088.4 missense, splice_region
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.403
• Publications: 0 publications found

Genes affected

CALB2 (HGNC:1435): (calbindin 2) This gene encodes an intracellular calcium-binding protein belonging to the troponin C superfamily. Members of this protein family have six EF-hand domains which bind calcium. This protein plays a role in diverse cellular functions, including message targeting and intracellular calcium buffering. It also functions as a modulator of neuronal excitability, and is a diagnostic marker for some human diseases, including Hirschsprung disease and some cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2010]

LINC02136 (HGNC:52995): (long intergenic non-protein coding RNA 2136)

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27770448).
• BP6: Variant 16-71385579-T-C is Benign according to our data. Variant chr16-71385579-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2613589.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007088.4. 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
	CALB2	NM_001740.5	MANE Select	c.630T>C	p.Asp210Asp	splice_region synonymous	Exon 10 of 11	NP_001731.2	A0A140VK08
	CALB2	NM_007088.4		c.536T>C	p.Ile179Thr	missense splice_region	Exon 8 of 9	NP_009019.1	A6NER6
	CALB2	NR_027910.3		n.660T>C		splice_region non_coding_transcript_exon	Exon 9 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALB2	ENST00000302628.9	TSL:1 MANE Select	c.630T>C	p.Asp210Asp	splice_region synonymous	Exon 10 of 11	ENSP00000307508.4	P22676
	CALB2	ENST00000349553.9	TSL:5	c.536T>C	p.Ile179Thr	missense splice_region	Exon 8 of 9	ENSP00000340294.5	A6NER6
	CALB2	ENST00000870349.1		c.747T>C	p.Asp249Asp	splice_region synonymous	Exon 11 of 12	ENSP00000540408.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461808 Hom.: 0 Cov.: 30 AF XY: 0.00000825 AC XY: 6 AN XY: 727208

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111962

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	2.2
DANN	Benign	0.91
DEOGEN2	Benign	0.076	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.14	N
M_CAP	Benign	0.072	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.74	T
PhyloP100		-0.40
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.0040	B
Vest4		0.40
MutPred		0.73		Gain of disorder (P = 0.0109)
MVP		0.68
ClinPred		0.11	T
GERP RS		-7.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2042560909; hg19: chr16-71419482;