rs7578199

Variant names:

• chr2-241253433-T-C
• rs7578199
• NM_005336.6:c.1253A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-241253433-T-C
• chr2-241253433-T-A
• chr2-241253433-T-G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_005336.6(HDLBP):​c.1253A>G​(p.Asn418Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 1,610,946 control chromosomes in the GnomAD database, including 40,645 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.21 (3605 hom., cov: 32)
  • Exomes 𝑓: 0.22 (37040 hom.)
• Consequence: HDLBP NM_005336.6 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0160
• Publications: 42 publications found

Genes affected

HDLBP (HGNC:4857): (high density lipoprotein binding protein) The protein encoded by this gene binds high density lipoprotein (HDL) and may function to regulate excess cholesterol levels in cells. The encoded protein also binds RNA and can induce heterochromatin formation. [provided by RefSeq, Mar 2016]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0039993525).
• BP6: Variant 2-241253433-T-C is Benign according to our data. Variant chr2-241253433-T-C is described in ClinVar as Benign. ClinVar VariationId is 3060902.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005336.6. 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
	HDLBP	NM_005336.6	MANE Select	c.1253A>G	p.Asn418Ser	missense	Exon 10 of 28	NP_005327.1	A0A024R4E5
	HDLBP	NM_001320965.3		c.1253A>G	p.Asn418Ser	missense	Exon 10 of 28	NP_001307894.1	Q00341-1
	HDLBP	NM_001320966.3		c.1253A>G	p.Asn418Ser	missense	Exon 10 of 28	NP_001307895.1	Q00341-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDLBP	ENST00000310931.10	TSL:1 MANE Select	c.1253A>G	p.Asn418Ser	missense	Exon 10 of 28	ENSP00000312042.4	Q00341-1
	HDLBP	ENST00000391975.5	TSL:1	c.1253A>G	p.Asn418Ser	missense	Exon 10 of 28	ENSP00000375836.1	Q00341-1
	HDLBP	ENST00000875612.1		c.1253A>G	p.Asn418Ser	missense	Exon 10 of 28	ENSP00000545671.1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31715 AN: 152030 Hom.: 3605 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0695

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.227

GnomAD2 exomes AF: 0.186 AC: 46672 AN: 251434 AF XY: 0.186

Gnomad AFR exome AF: 0.177

Gnomad AMR exome AF: 0.133

Gnomad ASJ exome AF: 0.302

Gnomad EAS exome AF: 0.00103

Gnomad FIN exome AF: 0.203

Gnomad NFE exome AF: 0.248

Gnomad OTH exome AF: 0.230

GnomAD4 exome AF: 0.215 AC: 314337 AN: 1458798 Hom.: 37040 Cov.: 31 AF XY: 0.213 AC XY: 154864 AN XY: 725912

African (AFR) AF: 0.180 AC: 6030 AN: 33430

American (AMR) AF: 0.138 AC: 6178 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 7740 AN: 26114

East Asian (EAS) AF: 0.000554 AC: 22 AN: 39700

South Asian (SAS) AF: 0.0719 AC: 6204 AN: 86242

European-Finnish (FIN) AF: 0.207 AC: 11038 AN: 53410

Middle Eastern (MID) AF: 0.275 AC: 1586 AN: 5758

European-Non Finnish (NFE) AF: 0.237 AC: 262789 AN: 1109152

Other (OTH) AF: 0.212 AC: 12750 AN: 60270

GnomAD4 genome AF: 0.208 AC: 31713 AN: 152148 Hom.: 3605 Cov.: 32 AF XY: 0.206 AC XY: 15317 AN XY: 74364

African (AFR) AF: 0.176 AC: 7287 AN: 41492

American (AMR) AF: 0.189 AC: 2884 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1051 AN: 3464

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5178

South Asian (SAS) AF: 0.0687 AC: 332 AN: 4830

European-Finnish (FIN) AF: 0.216 AC: 2285 AN: 10588

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16797 AN: 67982

Other (OTH) AF: 0.224 AC: 474 AN: 2116

Alfa AF: 0.234 Hom.: 14391

Bravo AF: 0.210

TwinsUK AF: 0.231 AC: 856

ALSPAC AF: 0.238 AC: 918

ESP6500AA AF: 0.183 AC: 805

ESP6500EA AF: 0.246 AC: 2118

ExAC AF: 0.187 AC: 22657

EpiCase AF: 0.270

EpiControl AF: 0.271

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	HDLBP-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.0060
DANN	Benign	0.38
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.76	T
MetaRNN	Benign	0.0040	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.016
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.068
Sift	Benign	0.18	T
Sift4G	Benign	0.26	T
Vest4		0.022
MPC		0.55
ClinPred		0.017	T
GERP RS		-12
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
gMVP		0.21
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7578199; hg19: chr2-242192848; COSMIC: COSV60493679; COSMIC: COSV60493679;