rs182221

Positions:

• chr16-56565309-C-G

Variant summary

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

The NM_032935.3(MT4):​c.31+150C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.732 in 672,270 control chromosomes in the GnomAD database, including 187,206 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 0.65 (35849 hom., cov: 32)
  • Exomes 𝑓: 0.76 (151357 hom.)
• Consequence: MT4 NM_032935.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.501

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MT4	NM_032935.3	c.31+150C>G		intron_variant		ENST00000219162.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT4	ENST00000219162.4	c.31+150C>G		intron_variant		1	NM_032935.3	P1
BBS2	ENST00000682930.1	c.42+5366G>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99382 AN: 152002 Hom.: 35849 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.876

Gnomad AMR AF: 0.790

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.575

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.784

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.799

Gnomad OTH AF: 0.683

GnomAD4 exome AF: 0.756 AC: 393018 AN: 520150 Hom.: 151357 AF XY: 0.754 AC XY: 203918 AN XY: 270400

Gnomad4 AFR exome AF: 0.318

Gnomad4 AMR exome AF: 0.816

Gnomad4 ASJ exome AF: 0.674

Gnomad4 EAS exome AF: 0.571

Gnomad4 SAS exome AF: 0.687

Gnomad4 FIN exome AF: 0.780

Gnomad4 NFE exome AF: 0.795

Gnomad4 OTH exome AF: 0.730

GnomAD4 genome AF: 0.653 AC: 99406 AN: 152120 Hom.: 35849 Cov.: 32 AF XY: 0.654 AC XY: 48610 AN XY: 74372

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.790

Gnomad4 ASJ AF: 0.682

Gnomad4 EAS AF: 0.574

Gnomad4 SAS AF: 0.675

Gnomad4 FIN AF: 0.784

Gnomad4 NFE AF: 0.799

Gnomad4 OTH AF: 0.681

Alfa AF: 0.711 Hom.: 5081

Bravo AF: 0.641

Asia WGS AF: 0.592 AC: 2060 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.46

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

LitVar

Other links and lift over

dbSNP: rs182221; hg19: chr16-56599221;