rs41278170

Positions:

• chr16-16150322-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The ENST00000205557.12(ABCC6):​c.4404-81C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00616 in 1,596,518 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0041 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0064 (34 hom.)
• Consequence: ABCC6 ENST00000205557.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.294

Genes affected

ABCC6 (HGNC:57): (ATP binding cassette subfamily C member 6) The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). The encoded protein, a member of the MRP subfamily, is involved in multi-drug resistance. Mutations in this gene cause pseudoxanthoma elasticum. Alternatively spliced transcript variants that encode different proteins have been described for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 16-16150322-G-A is Benign according to our data. Variant chr16-16150322-G-A is described in Lovd as [Benign].
• BS2: High Homozygotes in GnomAdExome4 at 34 AD,AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC6	NM_001171.6	c.4404-81C>T		intron_variant		ENST00000205557.12	NP_001162.5
ABCC6	NM_001351800.1	c.4062-81C>T		intron_variant			NP_001338729.1
ABCC6	NR_147784.1	n.4066-81C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC6	ENST00000205557.12	c.4404-81C>T		intron_variant		1	NM_001171.6	ENSP00000205557	P1
ABCC6	ENST00000456970.6	c.*1413-81C>T		intron_variant, NMD_transcript_variant		2		ENSP00000405002
ABCC6	ENST00000622290.5	c.*576-81C>T		intron_variant, NMD_transcript_variant		5		ENSP00000483331

Frequencies

GnomAD3 genomes AF: 0.00407 AC: 620 AN: 152248 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00166

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00386

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000941

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00679

Gnomad OTH AF: 0.00335

GnomAD4 exome AF: 0.00638 AC: 9211 AN: 1444152 Hom.: 34 AF XY: 0.00619 AC XY: 4439 AN XY: 717274

Gnomad4 AFR exome AF: 0.00102

Gnomad4 AMR exome AF: 0.00260

Gnomad4 ASJ exome AF: 0.00194

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000684

Gnomad4 FIN exome AF: 0.00171

Gnomad4 NFE exome AF: 0.00769

Gnomad4 OTH exome AF: 0.00621

GnomAD4 genome AF: 0.00407 AC: 620 AN: 152366 Hom.: 1 Cov.: 33 AF XY: 0.00387 AC XY: 288 AN XY: 74504

Gnomad4 AFR AF: 0.00166

Gnomad4 AMR AF: 0.00385

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.000941

Gnomad4 NFE AF: 0.00679

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00461 Hom.: 0

Bravo AF: 0.00424

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.4
DANN	Benign	0.68

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: rs41278170; hg19: chr16-16244179;