rs762604

chr16-56568759-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032935.3(MT4):c.98-82C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 959,410 control chromosomes in the GnomAD database, including 38,108 homozygotes. 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 0.21 (4470 hom., cov: 31)
  • Exomes 𝑓: 0.28 (33638 hom.)
• Consequence: MT4 NM_032935.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.120

Genes affected

MT4 (HGNC:18705): (metallothionein 4) Predicted to enable metal ion binding activity. Predicted to be involved in cellular response to metal ion; cellular zinc ion homeostasis; and detoxification of copper ion. Predicted to act upstream of or within cellular metal ion homeostasis. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

BBS2 (HGNC:967): (Bardet-Biedl syndrome 2) This gene is a member of the Bardet-Biedl syndrome (BBS) gene family. Bardet-Biedl syndrome is an autosomal recessive disorder characterized by severe pigmentary retinopathy, obesity, polydactyly, renal malformation and cognitive disability. The proteins encoded by BBS gene family members are structurally diverse and the similar phenotypes exhibited by mutations in BBS gene family members is likely due to their shared roles in cilia formation and function. Many BBS proteins localize to the basal bodies, ciliary axonemes, and pericentriolar regions of cells. BBS proteins may also be involved in intracellular trafficking via microtubule-related transport. The protein encoded by this gene forms a multiprotein BBSome complex with seven other BBS proteins.[provided by RefSeq, Oct 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MT4	NM_032935.3	c.98-82C>T		intron_variant		ENST00000219162.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT4	ENST00000219162.4	c.98-82C>T		intron_variant		1	NM_032935.3	P1
BBS2	ENST00000682930.1	c.42+1916G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32301 AN: 152014 Hom.: 4469 Cov.: 31

Gnomad AFR AF: 0.0530

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.0520

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.230

GnomAD4 exome AF: 0.276 AC: 223074 AN: 807278 Hom.: 33638 AF XY: 0.273 AC XY: 111791 AN XY: 409590

Gnomad4 AFR exome AF: 0.0476

Gnomad4 AMR exome AF: 0.152

Gnomad4 ASJ exome AF: 0.253

Gnomad4 EAS exome AF: 0.0722

Gnomad4 SAS exome AF: 0.122

Gnomad4 FIN exome AF: 0.331

Gnomad4 NFE exome AF: 0.311

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.212 AC: 32292 AN: 152132 Hom.: 4470 Cov.: 31 AF XY: 0.209 AC XY: 15578 AN XY: 74372

Gnomad4 AFR AF: 0.0529

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.0517

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.228

Alfa AF: 0.252 Hom.: 1470

Bravo AF: 0.196

Asia WGS AF: 0.0890 AC: 314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	14
Dann	Benign	0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs762604; hg19: chr16-56602671; COSMIC: COSV54642402;