rs57745014

Variant names:

• chr16-16155077-T-C
• rs57745014
• NM_001171.6:c.3883-46A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-16155077-T-C
• chr16-16155077-T-G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001171.6(ABCC6):​c.3883-46A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00371 in 1,533,288 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0038 (25 hom.)
• Consequence: ABCC6 NM_001171.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.16
• Publications: 2 publications found

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]

ABCC6 Gene-Disease associations (from GenCC):

• arterial calcification, generalized, of infancy, 2

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• autosomal recessive inherited pseudoxanthoma elasticum

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Laboratory for Molecular Medicine, Orphanet
• inherited pseudoxanthoma elasticum

  Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
• arterial calcification of infancy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 16-16155077-T-C is Benign according to our data. Variant chr16-16155077-T-C is described in ClinVar as Benign. ClinVar VariationId is 2646263.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 25 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001171.6. 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
	ABCC6	NM_001171.6	MANE Select	c.3883-46A>G		intron	N/A	NP_001162.5
	ABCC6	NM_001440309.1		c.3850-46A>G		intron	N/A	NP_001427238.1
	ABCC6	NM_001440310.1		c.3715-46A>G		intron	N/A	NP_001427239.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC6	ENST00000205557.12	TSL:1 MANE Select	c.3883-46A>G		intron	N/A	ENSP00000205557.7	O95255-1
	ABCC6	ENST00000909083.1		c.3979-46A>G		intron	N/A	ENSP00000579142.1
	ABCC6	ENST00000909090.1		c.3976-46A>G		intron	N/A	ENSP00000579149.1

Frequencies

GnomAD3 genomes AF: 0.00275 AC: 418 AN: 152154 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00950

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00422

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.00318 AC: 454 AN: 142966 AF XY: 0.00299

Gnomad AFR exome AF: 0.000387

Gnomad AMR exome AF: 0.000690

Gnomad ASJ exome AF: 0.0117

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00507

Gnomad NFE exome AF: 0.00461

Gnomad OTH exome AF: 0.00352

GnomAD4 exome AF: 0.00382 AC: 5270 AN: 1381016 Hom.: 25 Cov.: 31 AF XY: 0.00376 AC XY: 2555 AN XY: 679548

African (AFR) AF: 0.000382 AC: 12 AN: 31428

American (AMR) AF: 0.000732 AC: 26 AN: 35510

Ashkenazi Jewish (ASJ) AF: 0.0113 AC: 282 AN: 25024

East Asian (EAS) AF: 0.00 AC: 0 AN: 35464

South Asian (SAS) AF: 0.00110 AC: 87 AN: 79054

European-Finnish (FIN) AF: 0.00666 AC: 266 AN: 39948

Middle Eastern (MID) AF: 0.00159 AC: 9 AN: 5670

European-Non Finnish (NFE) AF: 0.00410 AC: 4398 AN: 1071446

Other (OTH) AF: 0.00331 AC: 190 AN: 57472

GnomAD4 genome AF: 0.00275 AC: 418 AN: 152272 Hom.: 0 Cov.: 31 AF XY: 0.00267 AC XY: 199 AN XY: 74454

African (AFR) AF: 0.000530 AC: 22 AN: 41548

American (AMR) AF: 0.000719 AC: 11 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00950 AC: 33 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.00565 AC: 60 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00422 AC: 287 AN: 68008

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.00481 Hom.: 0

Bravo AF: 0.00221

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.011
DANN	Benign	0.62
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs57745014; hg19: chr16-16248934;