NM_000519.4:c.180G>C

Variant names:

• chr11-5234126-C-G
• rs34626118
• NM_000519.4:c.180G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000519.4(HBD):​c.180G>C​(p.Lys60Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HBD NM_000519.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.692
• Publications: 0 publications found

Genes affected

HBD (HGNC:4829): (hemoglobin subunit delta) The delta (HBD) and beta (HBB) genes are normally expressed in the adult: two alpha chains plus two beta chains constitute HbA, which in normal adult life comprises about 97% of the total hemoglobin. Two alpha chains plus two delta chains constitute HbA-2, which with HbF comprises the remaining 3% of adult hemoglobin. Five beta-like globin genes are found within a 45 kb cluster on chromosome 11 in the following order: 5'-epsilon--Ggamma--Agamma--delta--beta-3'. Mutations in the delta-globin gene are associated with beta-thalassemia. [provided by RefSeq, Jul 2008]

HBD Gene-Disease associations (from GenCC):

• delta-beta-thalassemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000298932 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3970174).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000519.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBD	NM_000519.4	MANE Select	c.180G>C	p.Lys60Asn	missense	Exon 2 of 3	NP_000510.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBD	ENST00000650601.1	MANE Select	c.180G>C	p.Lys60Asn	missense	Exon 2 of 3	ENSP00000497529.1
	HBD	ENST00000643122.1		c.180G>C	p.Lys60Asn	missense	Exon 3 of 4	ENSP00000494708.1
	HBD	ENST00000292901.7	TSL:3	c.180G>C	p.Lys60Asn	missense	Exon 2 of 3	ENSP00000292901.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Uncertain	0.088	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.76	T
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.40	T
MetaSVM	Uncertain	0.18	D
MutationAssessor	Uncertain	2.7	M
PhyloP100		-0.69
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.58
Sift	Uncertain	0.012	D
Sift4G	Benign	0.13	T
Polyphen		0.53	P
Vest4		0.18
MutPred		0.70		Loss of methylation at K60 (P = 0.0112)
MVP		0.85
MPC		0.020
ClinPred		0.64	D
GERP RS		-2.5
PromoterAI		-0.00040	Neutral
Varity_R		0.61
gMVP		0.71
Mutation Taster		=4/96	disease causing

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: rs34626118; hg19: chr11-5255356;