rs2066738

Variant names:

• chr16-16154824-G-A
• rs2066738
• NM_001171.6:c.4042-30C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-16154824-G-A
• chr16-16154824-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001171.6(ABCC6):​c.4042-30C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,607,040 control chromosomes in the GnomAD database, including 29,556 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2198 hom., cov: 31)
  • Exomes 𝑓: 0.19 (27358 hom.)
• Consequence: ABCC6 NM_001171.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.51
• Publications: 6 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: Laboratory for Molecular Medicine, Orphanet, Labcorp Genetics (formerly Invitae), G2P
• arterial calcification of infancy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 16-16154824-G-A is Benign according to our data. Variant chr16-16154824-G-A is described in ClinVar as Benign. ClinVar VariationId is 1258776.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC6	NM_001171.6	c.4042-30C>T		intron_variant	Intron 28 of 30	ENST00000205557.12	NP_001162.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC6	ENST00000205557.12	c.4042-30C>T		intron_variant	Intron 28 of 30	1	NM_001171.6	ENSP00000205557.7
ABCC6	ENST00000456970.6	n.*1051-30C>T		intron_variant	Intron 26 of 28	2		ENSP00000405002.2
ABCC6	ENST00000576204.6	n.905-30C>T		intron_variant	Intron 1 of 1	5
ABCC6	ENST00000622290.5	n.*214-30C>T		intron_variant	Intron 29 of 31	5		ENSP00000483331.2

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23642 AN: 151918 Hom.: 2201 Cov.: 31

Gnomad AFR AF: 0.0679

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.147

GnomAD2 exomes AF: 0.209 AC: 49223 AN: 235266 AF XY: 0.212

Gnomad AFR exome AF: 0.0678

Gnomad AMR exome AF: 0.298

Gnomad ASJ exome AF: 0.157

Gnomad EAS exome AF: 0.184

Gnomad FIN exome AF: 0.241

Gnomad NFE exome AF: 0.178

Gnomad OTH exome AF: 0.194

GnomAD4 exome AF: 0.188 AC: 273075 AN: 1455004 Hom.: 27358 Cov.: 33 AF XY: 0.191 AC XY: 137991 AN XY: 723296

African (AFR) AF: 0.0625 AC: 2085 AN: 33374

American (AMR) AF: 0.285 AC: 12473 AN: 43804

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 3947 AN: 25930

East Asian (EAS) AF: 0.162 AC: 6386 AN: 39392

South Asian (SAS) AF: 0.305 AC: 25943 AN: 85186

European-Finnish (FIN) AF: 0.245 AC: 12858 AN: 52442

Middle Eastern (MID) AF: 0.196 AC: 1116 AN: 5700

European-Non Finnish (NFE) AF: 0.178 AC: 197217 AN: 1109146

Other (OTH) AF: 0.184 AC: 11050 AN: 60030

GnomAD4 genome AF: 0.156 AC: 23645 AN: 152036 Hom.: 2198 Cov.: 31 AF XY: 0.162 AC XY: 12027 AN XY: 74290

African (AFR) AF: 0.0678 AC: 2813 AN: 41508

American (AMR) AF: 0.191 AC: 2913 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 512 AN: 3468

East Asian (EAS) AF: 0.183 AC: 945 AN: 5154

South Asian (SAS) AF: 0.300 AC: 1441 AN: 4810

European-Finnish (FIN) AF: 0.246 AC: 2602 AN: 10570

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11960 AN: 67930

Other (OTH) AF: 0.146 AC: 309 AN: 2110

Alfa AF: 0.167 Hom.: 400

Bravo AF: 0.147

Asia WGS AF: 0.195 AC: 677 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.075
DANN	Benign	0.43
PhyloP100		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs2066738; hg19: chr16-16248681; COSMIC: COSV52742228;