rs41474449

chr9-104781415-TAAC-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005502.4(ABCA1):c.*2897_*2899del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,524 control chromosomes in the GnomAD database, including 1,187 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1187 hom., cov: 31)
  • Exomes 𝑓: 0.060 (0 hom.)
• Consequence: ABCA1 NM_005502.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.63

Genes affected

ABCA1 (HGNC:29): (ATP binding cassette subfamily A member 1) The membrane-associated 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 intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the ABC1 subfamily. Members of the ABC1 subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. With cholesterol as its substrate, this protein functions as a cholesteral efflux pump in the cellular lipid removal pathway. Mutations in both alleles of this gene cause Tangier disease and familial high-density lipoprotein (HDL) deficiency. [provided by RefSeq, Sep 2019]

NIPSNAP3B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 9-104781415-TAAC-T is Benign according to our data. Variant chr9-104781415-TAAC-T is described in ClinVar as [Benign]. Clinvar id is 1287228.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA1	NM_005502.4	c.*2897_*2899del		3_prime_UTR_variant	50/50	ENST00000374736.8
NIPSNAP3B	XR_007061325.1	n.960-6199_960-6197del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA1	ENST00000374736.8	c.*2897_*2899del		3_prime_UTR_variant	50/50	1	NM_005502.4	P1
ABCA1	ENST00000678995.1	c.*2897_*2899del		3_prime_UTR_variant	50/50

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16904 AN: 151974 Hom.: 1183 Cov.: 31

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.0726

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.0427

Gnomad FIN AF: 0.0629

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0775

Gnomad OTH AF: 0.111

GnomAD4 exome AF: 0.0602 AC: 26 AN: 432 Hom.: 0 AF XY: 0.0385 AC XY: 10 AN XY: 260

Gnomad4 FIN exome AF: 0.0610

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.111 AC: 16936 AN: 152092 Hom.: 1187 Cov.: 31 AF XY: 0.112 AC XY: 8310 AN XY: 74352

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.0726

Gnomad4 EAS AF: 0.251

Gnomad4 SAS AF: 0.0425

Gnomad4 FIN AF: 0.0629

Gnomad4 NFE AF: 0.0775

Gnomad4 OTH AF: 0.110

Alfa AF: 0.101 Hom.: 110

Bravo AF: 0.127

Asia WGS AF: 0.143 AC: 497 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 08, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs41474449; hg19: chr9-107543696;